5-35904586-C-A

Variant names:

• chr5-35904586-C-A
• rs201508660
• NM_001042625.2:c.586G>T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001042625.2(CAPSL):​c.586G>T​(p.Val196Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000174 in 1,613,818 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V196M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000092 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00018 (1 hom.)
• Consequence: CAPSL NM_001042625.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.60

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009449512).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAPSL	NM_001042625.2	c.586G>T	p.Val196Leu	missense_variant	Exon 5 of 5	ENST00000651391.1	NP_001036090.1
CAPSL	NM_144647.4	c.586G>T	p.Val196Leu	missense_variant	Exon 5 of 5		NP_653248.3
CAPSL	XM_006714444.4	c.637G>T	p.Val213Leu	missense_variant	Exon 5 of 5		XP_006714507.1
CAPSL	XM_006714445.4	c.*110G>T		3_prime_UTR_variant	Exon 5 of 5		XP_006714508.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAPSL	ENST00000651391.1	c.586G>T	p.Val196Leu	missense_variant	Exon 5 of 5		NM_001042625.2	ENSP00000498465.1
CAPSL	ENST00000397367.6	c.586G>T	p.Val196Leu	missense_variant	Exon 5 of 5	1		ENSP00000380524.2
CAPSL	ENST00000397366.5	c.586G>T	p.Val196Leu	missense_variant	Exon 5 of 5	3		ENSP00000380523.1
CAPSL	ENST00000513623.5	c.*16G>T		downstream_gene_variant		3		ENSP00000424806.1

Frequencies

GnomAD3 genomes AF: 0.0000922 AC: 14 AN: 151914 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000918

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00100 AC: 250 AN: 249284 Hom.: 2 AF XY: 0.000741 AC XY: 100 AN XY: 134926

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00712

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: 0.00

Gnomad OTH exome AF: 0.000654

GnomAD4 exome AF: 0.000182 AC: 266 AN: 1461786 Hom.: 1 Cov.: 31 AF XY: 0.000139 AC XY: 101 AN XY: 727208

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00593

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000921 AC: 14 AN: 152032 Hom.: 1 Cov.: 32 AF XY: 0.000135 AC XY: 10 AN XY: 74304

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000917

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000288 Hom.: 0

Bravo AF: 0.000510

ExAC AF: 0.000840 AC: 102

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.059	T;T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.96	.;D
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.0094	T;T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	1.2	L;L
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.081
Sift	Benign	0.12	T;T
Sift4G	Benign	0.25	T;T
Polyphen		0.0	B;B
Vest4		0.29
MutPred		0.52		Loss of MoRF binding (P = 0.1312);Loss of MoRF binding (P = 0.1312);
MVP		0.69
MPC		0.018
ClinPred		0.027	T
GERP RS		4.0
Varity_R		0.10
gMVP		0.67

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

Other links and lift over

dbSNP: rs201508660; hg19: chr5-35904688;