rs1258475561

Variant names:

• chr11-1597982-G-A
• rs1258475561
• NM_001004325.2:c.269C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-1597982-G-A
• chr11-1597982-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001004325.2(KRTAP5-2):​c.269C>T​(p.Ser90Phe) 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.

• Frequency: Genomes: not found (cov: 22)
• Consequence: KRTAP5-2 NM_001004325.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.493

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21836224).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP5-2	NM_001004325.2	c.269C>T	p.Ser90Phe	missense_variant	Exon 1 of 1	ENST00000412090.2	NP_001004325.1
KRTAP5-AS1	NR_021489.2	n.1063G>A		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.269C>T	p.Ser90Phe	missense_variant	Exon 1 of 1	6	NM_001004325.2	ENSP00000400041.1
KRTAP5-AS1	ENST00000424148.1	n.1063G>A		non_coding_transcript_exon_variant	Exon 2 of 2	2
KRTAP5-AS1	ENST00000659213.1	n.*74G>A		downstream_gene_variant

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 54

GnomAD4 genome Cov.: 22

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	12
DANN	Benign	0.94
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.096	N
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Pathogenic	3.4	M
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.062
Sift4G	Uncertain	0.0030	D
Polyphen		0.98	D
Vest4		0.36
MutPred		0.27		Loss of phosphorylation at S90 (P = 0.013);
MVP		0.16
MPC		0.096
ClinPred		0.62	D
GERP RS		2.8
Varity_R		0.25
gMVP		0.036

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: rs1258475561; hg19: chr11-1619212; COSMIC: COSV69015029; COSMIC: COSV69015029;