chr5-35921102-G-A

Position:

• chr5-35921102-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001042625.2(CAPSL):​c.19C>T​(p.His7Tyr) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CAPSL NM_001042625.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.26

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.759

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAPSL	NM_001042625.2	c.19C>T	p.His7Tyr	missense_variant	2/5	ENST00000651391.1	NP_001036090.1
CAPSL	NM_144647.4	c.19C>T	p.His7Tyr	missense_variant	2/5		NP_653248.3
CAPSL	XM_006714444.4	c.70C>T	p.His24Tyr	missense_variant	2/5		XP_006714507.1
CAPSL	XM_006714445.4	c.70C>T	p.His24Tyr	missense_variant	2/5		XP_006714508.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAPSL	ENST00000651391.1	c.19C>T	p.His7Tyr	missense_variant	2/5		NM_001042625.2	ENSP00000498465.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

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

Dec 05, 2024

The c.19C>T (p.H7Y) alteration is located in exon 2 (coding exon 1) of the CAPSL gene. This alteration results from a C to T substitution at nucleotide position 19, causing the histidine (H) at amino acid position 7 to be replaced by a tyrosine (Y). 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	Benign	0.22
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T;T;.;.
Eigen	Uncertain	0.68
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.90	.;D;D;D
M_CAP	Benign	0.026	D
MetaRNN	Pathogenic	0.76	D;D;D;D
MetaSVM	Uncertain	0.49	D
MutationAssessor	Uncertain	2.7	M;M;.;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-2.3	N;N;N;N
REVEL	Uncertain	0.60
Sift	Benign	0.31	T;T;T;T
Sift4G	Benign	0.34	T;T;D;D
Polyphen		0.99	D;D;.;.
Vest4		0.78
MutPred		0.32		Gain of phosphorylation at H7 (P = 0.0528);Gain of phosphorylation at H7 (P = 0.0528);Gain of phosphorylation at H7 (P = 0.0528);Gain of phosphorylation at H7 (P = 0.0528);
MVP		0.95
MPC		0.074
ClinPred		0.99	D
GERP RS		4.8
Varity_R		0.14
gMVP		0.76

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: chr5-35921204;