Genetic Variant XM_047430819.1:c.397C>T (chr13-33016046-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The XM_047430819.1(LOC124903151):c.397C>T(p.Pro133Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 152,232 control chromosomes in the GnomAD database, including 2,381 homozygotes. In-silico tool predicts a benign outcome for this variant. 4/4 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.17 ( 2381 hom., cov: 33)

Failed GnomAD Quality Control

Consequence

LOC124903151
XM_047430819.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0760

Publications

72 publications found

Variant links:

Genes affected

LOC124903151 (HGNC:):

LOC124903151 links:

KL (HGNC:6344): (klotho) This gene encodes a type-I membrane protein that is related to beta-glucosidases. Reduced production of this protein has been observed in patients with chronic renal failure (CRF), and this may be one of the factors underlying the degenerative processes (e.g., arteriosclerosis, osteoporosis, and skin atrophy) seen in CRF. Also, mutations within this protein have been associated with ageing and bone loss. [provided by RefSeq, Jul 2008]

KL Gene-Disease associations (from GenCC):

tumoral calcinosis, hyperphosphatemic, familial, 1
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
tumoral calcinosis, hyperphosphatemic, familial, 3
Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp

KL links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000830674.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank
ENSG00000308044	ENST00000830674.1	n.199C>T	non_coding_transcript_exon	Exon 1 of 2
ENSG00000308044	ENST00000830675.1	n.184C>T	non_coding_transcript_exon	Exon 1 of 2
ENSG00000308044	ENST00000830676.1	n.-33C>T	upstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.171

AC:

25965

AN:

152114

Hom.:

2377

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0927

Gnomad AMI

AF:

0.135

Gnomad AMR

AF:

0.217

Gnomad ASJ

AF:

0.189

Gnomad EAS

AF:

0.181

Gnomad SAS

AF:

0.171

Gnomad FIN

AF:

0.221

Gnomad MID

AF:

0.168

Gnomad NFE

AF:

0.199

Gnomad OTH

AF:

0.167

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.171

AC:

25972

AN:

152232

Hom.:

2381

Cov.:

AF XY:

0.172

AC XY:

12832

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.0927

AC:

3853

AN:

41562

American (AMR)

AF:

0.218

AC:

3329

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.189

AC:

657

AN:

3470

East Asian (EAS)

AF:

0.181

AC:

934

AN:

5156

South Asian (SAS)

AF:

0.169

AC:

818

AN:

4826

European-Finnish (FIN)

AF:

0.221

AC:

2347

AN:

10602

Middle Eastern (MID)

AF:

0.156

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.199

AC:

13516

AN:

67994

Other (OTH)

AF:

0.165

AC:

349

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1105

2211

3316

4422

5527

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

288

576

864

1152

1440

<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:

0.178

Hom.:

507

Bravo

AF:

0.168

Asia WGS

AF:

0.177

AC:

618

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

8.6

(source)

DANN

Benign

0.86

PhyloP100

0.076

PromoterAI

-0.051

Neutral

(source)

Splicing

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over