rs1243404110

Variant names:

• chr17-41065691-C-A
• rs1243404110
• NM_033184.4:c.155G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-41065691-C-A
• chr17-41065691-C-T

Variant summary

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

The NM_033184.4(KRTAP2-4):​c.155G>T​(p.Arg52Leu) 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: 30)
• Consequence: KRTAP2-4 NM_033184.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.06

Genes affected

KRTAP2-4 (HGNC:18891): (keratin associated protein 2-4) This protein is a member of the keratin-associated protein (KAP) family. The KAP proteins form a matrix of keratin intermediate filaments which contribute to the structure of hair fibers. KAP family members appear to have unique, family-specific amino- and carboxyl-terminal regions and are subdivided into three multi-gene families according to amino acid composition: the high sulfur, the ultrahigh sulfur, and the high tyrosine/glycine KAPs. This protein is a member of the high sulfur KAP family and the gene is localized to a cluster of KAPs at 17q12-q21. [provided by RefSeq, Jul 2008]

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=0.34064603).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP2-4	NM_033184.4	c.155G>T	p.Arg52Leu	missense_variant	Exon 1 of 1	ENST00000394015.3	NP_149440.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRTAP2-4	ENST00000394015.3	c.155G>T	p.Arg52Leu	missense_variant	Exon 1 of 1	6	NM_033184.4	ENSP00000377583.2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 30

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Uncertain	0.041	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.043	T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.96	D
M_CAP	Uncertain	0.096	D
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.47	T
PrimateAI	Pathogenic	0.79	T
PROVEAN	Pathogenic	-5.5	D
REVEL	Benign	0.28
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.035	D
Vest4		0.31
MutPred		0.60		Gain of catalytic residue at R52 (P = 0.0761);
MVP		0.55
MPC		1.7
ClinPred		0.98	D
GERP RS		5.5
Varity_R		0.49
gMVP		0.11

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: rs1243404110; hg19: chr17-39221943;