chr11-1598055-C-G

Variant names:

• chr11-1598055-C-G
• rs376100963
• NM_001004325.2:c.196G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001004325.2(KRTAP5-2):​c.196G>C​(p.Val66Leu) 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. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V66M) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 26)
• Consequence: KRTAP5-2 NM_001004325.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.846

Genes affected

KRTAP5-2 (HGNC:23597): (keratin associated protein 5-2) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

KRTAP5-AS1 (HGNC:27877): (KRTAP5-1/KRTAP5-2 antisense RNA 1)

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06566554).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP5-2	NM_001004325.2	c.196G>C	p.Val66Leu	missense_variant	Exon 1 of 1	ENST00000412090.2	NP_001004325.1
KRTAP5-AS1	NR_021489.2	n.1136C>G		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRTAP5-2	ENST00000412090.2	c.196G>C	p.Val66Leu	missense_variant	Exon 1 of 1	6	NM_001004325.2	ENSP00000400041.1
KRTAP5-AS1	ENST00000424148.1	n.1136C>G		non_coding_transcript_exon_variant	Exon 2 of 2	2
KRTAP5-AS1	ENST00000659213.1	n.*147C>G		downstream_gene_variant

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 26

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	7.5
DANN	Benign	0.83
DEOGEN2	Benign	0.059	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.017	N
M_CAP	Benign	0.0095	T
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Pathogenic	3.1	M
PROVEAN	Benign	-0.81	N
REVEL	Benign	0.050
Sift4G	Benign	0.31	T
Polyphen		0.067	B
Vest4		0.23
MutPred		0.13		Loss of ubiquitination at K64 (P = 0.0755);
MVP		0.21
MPC		0.086
ClinPred		0.15	T
GERP RS		0.82
Varity_R		0.22
gMVP		0.041

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

LitVar

Other links and lift over

dbSNP: rs376100963; hg19: chr11-1619285;