Variant 5-35904571-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001042625.2(CAPSL):c.601A>G(p.Met201Val) variant causes a missense change. The variant allele was found at a frequency of 0.00264 in 1,613,924 control chromosomes in the GnomAD database, including 113 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.014 ( 58 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 55 hom. )

Consequence

CAPSL
NM_001042625.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.96

Variant links:

Genes affected

CAPSL (HGNC:28375): (calcyphosine like) Predicted to enable calcium ion binding activity. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

CAPSL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003767997).

BP6

Variant 5-35904571-T-C is Benign according to our data. Variant chr5-35904571-T-C is described in ClinVar as [Benign]. Clinvar id is 787282.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0138 (2106/152158) while in subpopulation AFR AF= 0.0487 (2019/41492). AF 95% confidence interval is 0.0469. There are 58 homozygotes in gnomad4. There are 1002 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 58 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CAPSL	NM_001042625.2 linkuse as main transcript	c.601A>G	p.Met201Val	missense_variant	5/5	ENST00000651391.1
CAPSL	NM_144647.4 linkuse as main transcript	c.601A>G	p.Met201Val	missense_variant	5/5
CAPSL	XM_006714444.4 linkuse as main transcript	c.652A>G	p.Met218Val	missense_variant	5/5
CAPSL	XM_006714445.4 linkuse as main transcript	c.*125A>G		3_prime_UTR_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CAPSL	ENST00000651391.1 linkuse as main transcript	c.601A>G	p.Met201Val	missense_variant	5/5		NM_001042625.2	P1
CAPSL	ENST00000397367.6 linkuse as main transcript	c.601A>G	p.Met201Val	missense_variant	5/5	1		P1
CAPSL	ENST00000397366.5 linkuse as main transcript	c.601A>G	p.Met201Val	missense_variant	5/5	3		P1
CAPSL	ENST00000513623.5 linkuse as main transcript			downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0139

AC:

2106

AN:

152040

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0488

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00295

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00767

GnomAD3 exomes

AF:

0.00390

AC:

973

AN:

249630

Hom.:

AF XY:

0.00305

AC XY:

412

AN XY:

135084

show subpopulations

Gnomad AFR exome

AF:

0.0510

Gnomad AMR exome

AF:

0.00220

Gnomad ASJ exome

AF:

0.00477

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000152

Gnomad OTH exome

AF:

0.000654

GnomAD4 exome

AF:

0.00148

AC:

2159

AN:

1461766

Hom.:

Cov.:

AF XY:

0.00131

AC XY:

954

AN XY:

727194

show subpopulations

Gnomad4 AFR exome

AF:

0.0509

Gnomad4 AMR exome

AF:

0.00217

Gnomad4 ASJ exome

AF:

0.00532

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000540

Gnomad4 OTH exome

AF:

0.00253

GnomAD4 genome

AF:

0.0138

AC:

2106

AN:

152158

Hom.:

Cov.:

AF XY:

0.0135

AC XY:

1002

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.0487

Gnomad4 AMR

AF:

0.00294

Gnomad4 ASJ

AF:

0.00519

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00759

Alfa

AF:

0.00323

Hom.:

Bravo

AF:

0.0154

ESP6500AA

AF:

0.0481

AC:

212

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.00466

AC:

566

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 18, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.25

T;T

Eigen

Uncertain

0.20

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.88

.;D

MetaRNN

Benign

0.0038

T;T

MetaSVM

Benign

-0.84

MutationAssessor

Uncertain

2.3

M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-3.8

D;D

REVEL

Benign

0.19

Sift

Benign

0.055

T;T

Sift4G

Uncertain

0.050

T;T

Polyphen

0.022

B;B

Vest4

0.60

MVP

0.56

MPC

0.023

ClinPred

0.028

GERP RS

6.0

Varity_R

0.48

gMVP

0.78

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