5-35909912-C-G

Variant names:

• chr5-35909912-C-G
• NM_001042625.2:c.479G>C

Variant summary

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

The NM_001042625.2(CAPSL):​c.479G>C​(p.Arg160Thr) 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. 12/21 in silico tools predict a benign outcome for this variant. 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: 3.17

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=0.3445983).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAPSL	NM_001042625.2	c.479G>C	p.Arg160Thr	missense_variant	Exon 4 of 5	ENST00000651391.1	NP_001036090.1
CAPSL	NM_144647.4	c.479G>C	p.Arg160Thr	missense_variant	Exon 4 of 5		NP_653248.3
CAPSL	XM_006714444.4	c.530G>C	p.Arg177Thr	missense_variant	Exon 4 of 5		XP_006714507.1
CAPSL	XM_006714445.4	c.530G>C	p.Arg177Thr	missense_variant	Exon 4 of 5		XP_006714508.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAPSL	ENST00000651391.1	c.479G>C	p.Arg160Thr	missense_variant	Exon 4 of 5		NM_001042625.2	ENSP00000498465.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 18, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.479G>C (p.R160T) alteration is located in exon 4 (coding exon 3) of the CAPSL gene. This alteration results from a G to C substitution at nucleotide position 479, causing the arginine (R) at amino acid position 160 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	Benign	0.33
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Benign	21
DANN	Benign	0.90
DEOGEN2	Benign	0.37	T;T;.;.
Eigen	Benign	-0.0033
Eigen_PC	Benign	0.16
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.85	.;D;D;D
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.34	T;T;T;T
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	1.1	L;L;.;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-2.1	N;N;N;N
REVEL	Benign	0.26
Sift	Benign	0.50	T;T;T;T
Sift4G	Benign	0.52	T;T;T;T
Polyphen		0.097	B;B;.;.
Vest4		0.80
MutPred		0.45		Gain of ubiquitination at K161 (P = 0.0624);Gain of ubiquitination at K161 (P = 0.0624);Gain of ubiquitination at K161 (P = 0.0624);Gain of ubiquitination at K161 (P = 0.0624);
MVP		0.74
MPC		0.020
ClinPred		0.52	D
GERP RS		5.7
Varity_R		0.34
gMVP		0.69

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: chr5-35910014;