5-35904586-C-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -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. 14/22 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
• Publications: 2 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042625.2. 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
	CAPSL	NM_001042625.2	MANE Select	c.586G>T	p.Val196Leu	missense	Exon 5 of 5	NP_001036090.1	Q8WWF8
	CAPSL	NM_144647.4		c.586G>T	p.Val196Leu	missense	Exon 5 of 5	NP_653248.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAPSL	ENST00000651391.1	MANE Select	c.586G>T	p.Val196Leu	missense	Exon 5 of 5	ENSP00000498465.1	Q8WWF8
	CAPSL	ENST00000397367.6	TSL:1	c.586G>T	p.Val196Leu	missense	Exon 5 of 5	ENSP00000380524.2	Q8WWF8
	CAPSL	ENST00000397366.5	TSL:3	c.586G>T	p.Val196Leu	missense	Exon 5 of 5	ENSP00000380523.1	Q8WWF8

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

GnomAD2 exomes AF: 0.00100 AC: 250 AN: 249284 AF XY: 0.000741

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 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

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00593 AC: 265 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111950

Other (OTH) AF: 0.00 AC: 0 AN: 60392

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

African (AFR) AF: 0.00 AC: 0 AN: 41484

American (AMR) AF: 0.000917 AC: 14 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.00 AC: 0 AN: 4766

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10582

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68000

Other (OTH) AF: 0.00 AC: 0 AN: 2106

Alfa AF: 0.0000569 Hom.: 0

Bravo AF: 0.000510

ExAC AF: 0.000840 AC: 102

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
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
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	1.2	L
PhyloP100		1.6
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.081
Sift	Benign	0.12	T
Sift4G	Benign	0.25	T
Polyphen		0.0	B
Vest4		0.29
MutPred		0.52		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
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs201508660; hg19: chr5-35904688;