chr5-35910427-C-G

Variant names:

• chr5-35910427-C-G
• rs1445898
• NM_001042625.2:c.254G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001042625.2(CAPSL):​c.254G>C​(p.Arg85Pro) 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. 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: Not reported in ClinVar
• Conservation: PhyloP100: -0.981
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1412166).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAPSL	NM_001042625.2	c.254G>C	p.Arg85Pro	missense_variant	Exon 3 of 5	ENST00000651391.1	NP_001036090.1
CAPSL	NM_144647.4	c.254G>C	p.Arg85Pro	missense_variant	Exon 3 of 5		NP_653248.3
CAPSL	XM_006714444.4	c.305G>C	p.Arg102Pro	missense_variant	Exon 3 of 5		XP_006714507.1
CAPSL	XM_006714445.4	c.305G>C	p.Arg102Pro	missense_variant	Exon 3 of 5		XP_006714508.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAPSL	ENST00000651391.1	c.254G>C	p.Arg85Pro	missense_variant	Exon 3 of 5		NM_001042625.2	ENSP00000498465.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.81
BayesDel_addAF	Uncertain	0.034	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	17
DANN	Benign	0.77
DEOGEN2	Benign	0.30	T;T;.;.
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.14	N
LIST_S2	Uncertain	0.94	.;D;D;D
M_CAP	Benign	0.070	D
MetaRNN	Benign	0.14	T;T;T;T
MetaSVM	Benign	-0.55	T
MutationAssessor	Pathogenic	3.1	M;M;.;.
PhyloP100		-0.98
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.5	N;N;N;N
REVEL	Uncertain	0.37
Sift	Benign	0.091	T;T;T;T
Sift4G	Benign	0.27	T;T;T;T
Polyphen		0.0040	B;B;.;.
Vest4		0.64
MutPred		0.48		Gain of ubiquitination at K89 (P = 0.0843);Gain of ubiquitination at K89 (P = 0.0843);Gain of ubiquitination at K89 (P = 0.0843);Gain of ubiquitination at K89 (P = 0.0843);
MVP		0.36
MPC		0.026
ClinPred		0.11	T
GERP RS		0.53
Varity_R		0.80
gMVP		0.88
Mutation Taster		=76/24	polymorphism

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

Other links and lift over

dbSNP: rs1445898; hg19: chr5-35910529;