5-35910427-C-T

Position:

• chr5-35910427-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001042625.2(CAPSL):​c.254G>A​(p.Arg85Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 1,612,522 control chromosomes in the GnomAD database, including 180,477 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.43 (14975 hom., cov: 32)
  • Exomes 𝑓: 0.47 (165502 hom.)
• Consequence: CAPSL NM_001042625.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.981

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.4780674E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAPSL	NM_001042625.2	c.254G>A	p.Arg85Gln	missense_variant	3/5	ENST00000651391.1	NP_001036090.1
CAPSL	NM_144647.4	c.254G>A	p.Arg85Gln	missense_variant	3/5		NP_653248.3
CAPSL	XM_006714444.4	c.305G>A	p.Arg102Gln	missense_variant	3/5		XP_006714507.1
CAPSL	XM_006714445.4	c.305G>A	p.Arg102Gln	missense_variant	3/5		XP_006714508.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAPSL	ENST00000651391.1	c.254G>A	p.Arg85Gln	missense_variant	3/5		NM_001042625.2	ENSP00000498465.1

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64658 AN: 151864 Hom.: 14953 Cov.: 32

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.746

Gnomad SAS AF: 0.671

Gnomad FIN AF: 0.493

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.443

Gnomad OTH AF: 0.432

GnomAD3 exomes AF: 0.515 AC: 129341 AN: 251170 Hom.: 35965 AF XY: 0.517 AC XY: 70212 AN XY: 135770

Gnomad AFR exome AF: 0.263

Gnomad AMR exome AF: 0.685

Gnomad ASJ exome AF: 0.430

Gnomad EAS exome AF: 0.745

Gnomad SAS exome AF: 0.659

Gnomad FIN exome AF: 0.490

Gnomad NFE exome AF: 0.437

Gnomad OTH exome AF: 0.493

GnomAD4 exome AF: 0.466 AC: 680992 AN: 1460540 Hom.: 165502 Cov.: 37 AF XY: 0.472 AC XY: 342963 AN XY: 726624

Gnomad4 AFR exome AF: 0.265

Gnomad4 AMR exome AF: 0.667

Gnomad4 ASJ exome AF: 0.436

Gnomad4 EAS exome AF: 0.772

Gnomad4 SAS exome AF: 0.656

Gnomad4 FIN exome AF: 0.489

Gnomad4 NFE exome AF: 0.438

Gnomad4 OTH exome AF: 0.476

GnomAD4 genome AF: 0.426 AC: 64719 AN: 151982 Hom.: 14975 Cov.: 32 AF XY: 0.437 AC XY: 32468 AN XY: 74276

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.545

Gnomad4 ASJ AF: 0.435

Gnomad4 EAS AF: 0.745

Gnomad4 SAS AF: 0.672

Gnomad4 FIN AF: 0.493

Gnomad4 NFE AF: 0.443

Gnomad4 OTH AF: 0.439

Alfa AF: 0.447 Hom.: 40492

Bravo AF: 0.419

TwinsUK AF: 0.441 AC: 1635

ALSPAC AF: 0.446 AC: 1720

ESP6500AA AF: 0.277 AC: 1220

ESP6500EA AF: 0.444 AC: 3821

ExAC AF: 0.505 AC: 61323

Asia WGS AF: 0.688 AC: 2393 AN: 3478

EpiCase AF: 0.433

EpiControl AF: 0.431

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	7.3
DANN	Benign	0.81
DEOGEN2	Benign	0.063	T;T;.;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.041	N
LIST_S2	Benign	0.77	.;T;T;T
MetaRNN	Benign	0.0000015	T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.55	N;N;.;.
PrimateAI	Benign	0.23	T
PROVEAN	Benign	0.83	N;N;N;N
REVEL	Benign	0.091
Sift	Benign	0.47	T;T;T;T
Sift4G	Benign	0.59	T;T;T;T
Polyphen		0.0010	B;B;.;.
Vest4		0.068
MPC		0.019
ClinPred		0.00077	T
GERP RS		0.53
Varity_R		0.035
gMVP		0.43

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: rs1445898; hg19: chr5-35910529;