5-35921074-T-G

Variant names:

• chr5-35921074-T-G
• NM_001042625.2:c.47A>C

Variant summary

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

The NM_001042625.2(CAPSL):​c.47A>C​(p.Lys16Thr) variant causes a missense change. 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: 3.76

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=0.39782995).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAPSL	NM_001042625.2	c.47A>C	p.Lys16Thr	missense_variant	Exon 2 of 5	ENST00000651391.1	NP_001036090.1
CAPSL	NM_144647.4	c.47A>C	p.Lys16Thr	missense_variant	Exon 2 of 5		NP_653248.3
CAPSL	XM_006714444.4	c.98A>C	p.Lys33Thr	missense_variant	Exon 2 of 5		XP_006714507.1
CAPSL	XM_006714445.4	c.98A>C	p.Lys33Thr	missense_variant	Exon 2 of 5		XP_006714508.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAPSL	ENST00000651391.1	c.47A>C	p.Lys16Thr	missense_variant	Exon 2 of 5		NM_001042625.2	ENSP00000498465.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 15, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.47A>C (p.K16T) alteration is located in exon 2 (coding exon 1) of the CAPSL gene. This alteration results from a A to C substitution at nucleotide position 47, causing the lysine (K) at amino acid position 16 to be replaced by a threonine (T). 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	Uncertain	0.36
BayesDel_addAF	Uncertain	0.098	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T;T;.;.
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.79	.;T;T;T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.40	T;T;T;T
MetaSVM	Benign	-0.53	T
MutationAssessor	Benign	1.6	L;L;.;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-2.2	N;N;N;N
REVEL	Uncertain	0.41
Sift	Benign	0.23	T;T;T;T
Sift4G	Benign	0.53	T;T;T;T
Polyphen		0.017	B;B;.;.
Vest4		0.68
MutPred		0.49		Gain of phosphorylation at K16 (P = 0.0137);Gain of phosphorylation at K16 (P = 0.0137);Gain of phosphorylation at K16 (P = 0.0137);Gain of phosphorylation at K16 (P = 0.0137);
MVP		0.80
MPC		0.020
ClinPred		0.72	D
GERP RS		3.6
Varity_R		0.17
gMVP		0.77

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-35921176; COSMIC: COSV68437787;