Variant chr5-35909961-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001042625.2(CAPSL):c.430C>T(p.His144Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000616 in 1,461,554 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

CAPSL
NM_001042625.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.03

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19324183).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAPSL	NM_001042625.2 linkuse as main transcript	c.430C>T	p.His144Tyr	missense_variant	4/5	ENST00000651391.1	NP_001036090.1	Q8WWF8
CAPSL	NM_144647.4 linkuse as main transcript	c.430C>T	p.His144Tyr	missense_variant	4/5		NP_653248.3	Q8WWF8
CAPSL	XM_006714444.4 linkuse as main transcript	c.481C>T	p.His161Tyr	missense_variant	4/5		XP_006714507.1
CAPSL	XM_006714445.4 linkuse as main transcript	c.481C>T	p.His161Tyr	missense_variant	4/5		XP_006714508.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAPSL	ENST00000651391.1 linkuse as main transcript	c.430C>T	p.His144Tyr	missense_variant	4/5		NM_001042625.2	ENSP00000498465.1		Q8WWF8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251108

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135708

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461554

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727040

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000719

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 01, 2022

The c.430C>T (p.H144Y) alteration is located in exon 4 (coding exon 3) of the CAPSL gene. This alteration results from a C to T substitution at nucleotide position 430, causing the histidine (H) at amino acid position 144 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.35

T;T;.;.

Eigen

Benign

-0.086

Eigen_PC

Benign

0.097

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.82

.;T;D;D

M_CAP

Benign

0.022

MetaRNN

Benign

0.19

T;T;T;T

MetaSVM

Benign

-0.78

MutationAssessor

Benign

0.92

L;L;.;.

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-2.4

N;N;N;D

REVEL

Benign

0.14

Sift

Benign

0.20

T;T;T;T

Sift4G

Benign

0.25

T;T;T;T

Polyphen

0.0010

B;B;.;.

Vest4

0.35

MutPred

0.35

Loss of disorder (P = 0.0493);Loss of disorder (P = 0.0493);Loss of disorder (P = 0.0493);Loss of disorder (P = 0.0493);

MVP

0.65

MPC

0.019

ClinPred

0.22

GERP RS

5.6

Varity_R

0.25

gMVP

0.58

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