5-35910481-C-T

Position:

• chr5-35910481-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001042625.2(CAPSL):​c.200G>A​(p.Gly67Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CAPSL NM_001042625.2 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 7.38

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.861

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAPSL	NM_001042625.2	c.200G>A	p.Gly67Glu	missense_variant	3/5	ENST00000651391.1	NP_001036090.1
CAPSL	NM_144647.4	c.200G>A	p.Gly67Glu	missense_variant	3/5		NP_653248.3
CAPSL	XM_006714444.4	c.251G>A	p.Gly84Glu	missense_variant	3/5		XP_006714507.1
CAPSL	XM_006714445.4	c.251G>A	p.Gly84Glu	missense_variant	3/5		XP_006714508.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAPSL	ENST00000651391.1	c.200G>A	p.Gly67Glu	missense_variant	3/5		NM_001042625.2	ENSP00000498465.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Autism Uncertain:1

Uncertain significance, no assertion criteria provided

research

Centre for Addiction & Mental Health, Centre for Addiction & Mental Health

-

Gene not previously associated with disease; independent supportng evidence needed -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.28
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.42	T;T;.;.
Eigen	Pathogenic	0.91
Eigen_PC	Pathogenic	0.84
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	.;D;D;D
M_CAP	Uncertain	0.14	D
MetaRNN	Pathogenic	0.86	D;D;D;D
MetaSVM	Uncertain	0.48	D
MutationAssessor	Pathogenic	3.2	M;M;.;.
PrimateAI	Pathogenic	0.80	T
PROVEAN	Pathogenic	-7.9	D;D;D;D
REVEL	Pathogenic	0.87
Sift	Uncertain	0.0010	D;D;D;D
Sift4G	Uncertain	0.0020	D;D;D;D
Polyphen		1.0	D;D;.;.
Vest4		0.96
MutPred		0.61		Loss of catalytic residue at D70 (P = 0.0662);Loss of catalytic residue at D70 (P = 0.0662);Loss of catalytic residue at D70 (P = 0.0662);Loss of catalytic residue at D70 (P = 0.0662);
MVP		0.93
MPC		0.16
ClinPred		1.0	D
GERP RS		5.3
Varity_R		0.99
gMVP		0.95

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr5-35910583; COSMIC: COSV68438109;