chr11-13492506-G-T

Position:

chr11-13492506-G-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000315.4(PTH):c.247C>A(p.Arg83=) 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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 255817.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-13492506-G-T is described in Lovd as [Benign].

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTH	NM_000315.4 linkuse as main transcript	c.247C>A	p.Arg83=	synonymous_variant	3/3	ENST00000282091.6
PTH	NM_001316352.2 linkuse as main transcript	c.343C>A	p.Arg115=	synonymous_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTH	ENST00000282091.6 linkuse as main transcript	c.247C>A	p.Arg83=	synonymous_variant	3/3	1	NM_000315.4	P1
PTH	ENST00000529816.1 linkuse as main transcript	c.247C>A	p.Arg83=	synonymous_variant	3/3	5		P1

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

GnomAD3 exomes

AF:

0.157

AC:

39536

AN:

251396

Hom.:

3803

AF XY:

0.170

AC XY:

23102

AN XY:

135866

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 SAS exome

AF:

0.323

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

Gnomad4 AFR exome

AF:

0.0663

Gnomad4 AMR exome

AF:

0.0810

Gnomad4 ASJ exome

AF:

0.201

Gnomad4 EAS exome

AF:

0.112

Gnomad4 SAS exome

AF:

0.319

Gnomad4 FIN exome

AF:

0.140

Gnomad4 NFE exome

AF:

0.153

Gnomad4 OTH exome

AF:

0.164

GnomAD4 genome

AF:

0.130

AC:

19751

AN:

151482

Hom.:

1515

Cov.:

AF XY:

0.134

AC XY:

9919

AN XY:

73974

show subpopulations

Gnomad4 AFR

AF:

0.0666

Gnomad4 AMR

AF:

0.118

Gnomad4 ASJ

AF:

0.185

Gnomad4 EAS

AF:

0.125

Gnomad4 SAS

AF:

0.321

Gnomad4 FIN

AF:

0.135

Gnomad4 NFE

AF:

0.155

Gnomad4 OTH

AF:

0.150

Alfa

AF:

0.125

Hom.:

576

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Hypoparathyroidism, familial isolated 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

Familial hypoparathyroidism

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Mar 06, 2018

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

4.8

DANN

Benign

0.64

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over