5-35910067-C-A

Position:

• chr5-35910067-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001042625.2(CAPSL):​c.324G>T​(p.Met108Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CAPSL NM_001042625.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.48

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAPSL	NM_001042625.2	c.324G>T	p.Met108Ile	missense_variant	4/5	ENST00000651391.1
CAPSL	NM_144647.4	c.324G>T	p.Met108Ile	missense_variant	4/5
CAPSL	XM_006714444.4	c.375G>T	p.Met125Ile	missense_variant	4/5
CAPSL	XM_006714445.4	c.375G>T	p.Met125Ile	missense_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAPSL	ENST00000651391.1	c.324G>T	p.Met108Ile	missense_variant	4/5		NM_001042625.2	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Oct 06, 2023

The c.324G>T (p.M108I) alteration is located in exon 4 (coding exon 3) of the CAPSL gene. This alteration results from a G to T substitution at nucleotide position 324, causing the methionine (M) at amino acid position 108 to be replaced by an isoleucine (I). 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	0.86
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T;T;.;.
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	.;D;D;D
M_CAP	Uncertain	0.086	D
MetaRNN	Uncertain	0.62	D;D;D;D
MetaSVM	Benign	-0.45	T
MutationAssessor	Uncertain	2.5	M;M;.;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-3.6	D;D;D;D
REVEL	Uncertain	0.41
Sift	Uncertain	0.0030	D;D;D;D
Sift4G	Uncertain	0.014	D;D;D;D
Polyphen		0.63	P;P;.;.
Vest4		0.74
MutPred		0.48		Gain of catalytic residue at M108 (P = 0.0146);Gain of catalytic residue at M108 (P = 0.0146);Gain of catalytic residue at M108 (P = 0.0146);Gain of catalytic residue at M108 (P = 0.0146);
MVP		0.74
MPC		0.12
ClinPred		0.99	D
GERP RS		5.7
Varity_R		0.72
gMVP		0.71

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-35910169;