5-35921025-C-G

Position:

• chr5-35921025-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001042625.2(CAPSL):​c.96G>C​(p.Gln32His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CAPSL NM_001042625.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.325

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34707424).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAPSL	NM_001042625.2	c.96G>C	p.Gln32His	missense_variant	2/5	ENST00000651391.1	NP_001036090.1
CAPSL	NM_144647.4	c.96G>C	p.Gln32His	missense_variant	2/5		NP_653248.3
CAPSL	XM_006714444.4	c.147G>C	p.Gln49His	missense_variant	2/5		XP_006714507.1
CAPSL	XM_006714445.4	c.147G>C	p.Gln49His	missense_variant	2/5		XP_006714508.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAPSL	ENST00000651391.1	c.96G>C	p.Gln32His	missense_variant	2/5		NM_001042625.2	ENSP00000498465.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 05, 2023

The c.96G>C (p.Q32H) alteration is located in exon 2 (coding exon 1) of the CAPSL gene. This alteration results from a G to C substitution at nucleotide position 96, causing the glutamine (Q) at amino acid position 32 to be replaced by a histidine (H). 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	Pathogenic	0.59
BayesDel_addAF	Uncertain	0.053	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.24	T;T;.;.
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.57	D
LIST_S2	Uncertain	0.97	.;D;D;D
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.35	T;T;T;T
MetaSVM	Benign	-0.30	T
MutationAssessor	Uncertain	2.9	M;M;.;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-3.2	D;D;D;D
REVEL	Uncertain	0.41
Sift	Benign	0.12	T;T;T;T
Sift4G	Benign	0.28	T;T;T;T
Polyphen		0.016	B;B;.;.
Vest4		0.41
MutPred		0.37		Loss of MoRF binding (P = 0.0912);Loss of MoRF binding (P = 0.0912);Loss of MoRF binding (P = 0.0912);Loss of MoRF binding (P = 0.0912);
MVP		0.84
MPC		0.018
ClinPred		0.87	D
GERP RS		2.0
Varity_R		0.24
gMVP		0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs767009111; hg19: chr5-35921127;