17-41167721-C-T

Variant names:

• chr17-41167721-C-T
• rs368282974
• NM_033187.2:c.452G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_033187.2(KRTAP4-3):​c.452G>A​(p.Arg151His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000131 in 1,613,528 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (1 hom.)
• Consequence: KRTAP4-3 NM_033187.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.71
• Publications: 4 publications found

Genes affected

KRTAP4-3 (HGNC:18908): (keratin associated protein 4-3) Involved in aging and hair cycle. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.061731547).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP4-3	NM_033187.2	c.452G>A	p.Arg151His	missense_variant	Exon 1 of 1	ENST00000391356.4	NP_149443.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRTAP4-3	ENST00000391356.4	c.452G>A	p.Arg151His	missense_variant	Exon 1 of 1	6	NM_033187.2	ENSP00000375151.2

Frequencies

GnomAD3 genomes AF: 0.000237 AC: 36 AN: 152126 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000580

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000169 AC: 42 AN: 248616 AF XY: 0.000178

Gnomad AFR exome AF: 0.000393

Gnomad AMR exome AF: 0.000175

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000278

Gnomad NFE exome AF: 0.000133

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.000120 AC: 175 AN: 1461402 Hom.: 1 Cov.: 31 AF XY: 0.000131 AC XY: 95 AN XY: 726966

African (AFR) AF: 0.000509 AC: 17 AN: 33406

American (AMR) AF: 0.000157 AC: 7 AN: 44596

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.000220 AC: 19 AN: 86220

European-Finnish (FIN) AF: 0.000300 AC: 16 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 0.0000962 AC: 107 AN: 1111824

Other (OTH) AF: 0.000149 AC: 9 AN: 60386

GnomAD4 genome AF: 0.000237 AC: 36 AN: 152126 Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 14 AN XY: 74314

African (AFR) AF: 0.000580 AC: 24 AN: 41386

American (AMR) AF: 0.0000655 AC: 1 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000229 Hom.: 0

Bravo AF: 0.000295

ESP6500AA AF: 0.000237 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000231 AC: 28

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 11, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.452G>A (p.R151H) alteration is located in exon 1 (coding exon 1) of the KRTAP4-3 gene. This alteration results from a G to A substitution at nucleotide position 452, causing the arginine (R) at amino acid position 151 to be replaced by a histidine (H). 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	0.11
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.36
DANN	Benign	0.87
DEOGEN2	Benign	0.010	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0083	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		-1.7
PrimateAI	Benign	0.17	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.036
Sift	Benign	0.065	T
Sift4G	Benign	0.070	T
Polyphen		0.028	B
Vest4		0.080
MVP		0.081
MPC		0.026
ClinPred		0.020	T
GERP RS		-2.3
PromoterAI		-0.0014	Neutral
Varity_R		0.053
gMVP		0.053
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs368282974; hg19: chr17-39323973; COSMIC: COSV101194139;