11-13492506-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000315.4(PTH):c.247C>A(p.Arg83Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 1,613,284 control chromosomes in the GnomAD database, including 21,820 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1515 hom., cov: 32)

Exomes 𝑓: 0.16 ( 20305 hom. )

Consequence

PTH
NM_000315.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.05

Publications

49 publications found

Variant links:

Genes affected

PTH (HGNC:9606): (parathyroid hormone) This gene encodes a member of the parathyroid family of proteins. The encoded preproprotein is proteolytically processed to generate a protein that binds to the parathyroid hormone/parathyroid hormone-related peptide receptor and regulates blood calcium and phosphate levels. Excess production of the encoded protein, known as hyperparathyroidism, can result in hypercalcemia and kidney stones. On the other hand, defective processing of the encoded protein may lead to hypoparathyroidism, which can result in hypocalcemia and numbness. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]

PTH Gene-Disease associations (from GenCC):

hypoparathyroidism, familial isolated 1
Inheritance: AD, AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
familial isolated hypoparathyroidism due to impaired PTH secretion
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

PTH links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 11-13492506-G-T is Benign according to our data. Variant chr11-13492506-G-T is described in ClinVar as Benign. ClinVar VariationId is 255817.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.05 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000315.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTH	NM_000315.4	MANE Select	c.247C>A	p.Arg83Arg	synonymous	Exon 3 of 3	NP_000306.1
	PTH	NM_001316352.2		c.343C>A	p.Arg115Arg	synonymous	Exon 3 of 3	NP_001303281.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTH	ENST00000282091.6	TSL:1 MANE Select	c.247C>A	p.Arg83Arg	synonymous	Exon 3 of 3	ENSP00000282091.1
	PTH	ENST00000529816.1	TSL:5	c.247C>A	p.Arg83Arg	synonymous	Exon 3 of 3	ENSP00000433208.1

Frequencies

GnomAD3 genomes

AF:

0.130

AC:

19741

AN:

151362

Hom.:

1511

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0668

Gnomad AMI

AF:

0.0538

Gnomad AMR

AF:

0.119

Gnomad ASJ

AF:

0.185

Gnomad EAS

AF:

0.125

Gnomad SAS

AF:

0.320

Gnomad FIN

AF:

0.135

Gnomad MID

AF:

0.256

Gnomad NFE

AF:

0.155

Gnomad OTH

AF:

0.148

GnomAD2 exomes

AF:

0.157

AC:

39536

AN:

251396

AF XY:

0.170

show subpopulations

Gnomad AFR exome

AF:

0.0631

Gnomad AMR exome

AF:

0.0767

Gnomad ASJ exome

AF:

0.200

Gnomad EAS exome

AF:

0.120

Gnomad FIN exome

AF:

0.133

Gnomad NFE exome

AF:

0.157

Gnomad OTH exome

AF:

0.162

GnomAD4 exome

AF:

0.159

AC:

232296

AN:

1461802

Hom.:

20305

Cov.:

AF XY:

0.165

AC XY:

119645

AN XY:

727204

show subpopulations

African (AFR)

AF:

0.0663

AC:

2219

AN:

33474

American (AMR)

AF:

0.0810

AC:

3622

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.201

AC:

5264

AN:

26134

East Asian (EAS)

AF:

0.112

AC:

4464

AN:

39696

South Asian (SAS)

AF:

0.319

AC:

27552

AN:

86256

European-Finnish (FIN)

AF:

0.140

AC:

7469

AN:

53410

Middle Eastern (MID)

AF:

0.235

AC:

1353

AN:

5766

European-Non Finnish (NFE)

AF:

0.153

AC:

170447

AN:

1111954

Other (OTH)

AF:

0.164

AC:

9906

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

12183

24366

36548

48731

60914

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6138

12276

18414

24552

30690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.130

AC:

19751

AN:

151482

Hom.:

1515

Cov.:

AF XY:

0.134

AC XY:

9919

AN XY:

73974

show subpopulations

African (AFR)

AF:

0.0666

AC:

2749

AN:

41284

American (AMR)

AF:

0.118

AC:

1800

AN:

15204

Ashkenazi Jewish (ASJ)

AF:

0.185

AC:

642

AN:

3462

East Asian (EAS)

AF:

0.125

AC:

641

AN:

5142

South Asian (SAS)

AF:

0.321

AC:

1535

AN:

4784

European-Finnish (FIN)

AF:

0.135

AC:

1412

AN:

10424

Middle Eastern (MID)

AF:

0.264

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.155

AC:

10530

AN:

67878

Other (OTH)

AF:

0.150

AC:

316

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

863

1727

2590

3454

4317

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

246

492

738

984

1230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.127

Hom.:

817

Bravo

AF:

0.122

EpiCase

AF:

0.165

EpiControl

AF:

0.164

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Hypoparathyroidism, familial isolated 1

Benign:1

Nov 07, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Familial hypoparathyroidism

Benign:1

Mar 06, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

4.8

(source)

DANN

Benign

0.64

PhyloP100

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over