17-41097708-C-T

Variant names:

• chr17-41097708-C-T
• rs80168553
• NM_031960.3:c.377G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031960.3(KRTAP4-8):​c.377G>A​(p.Arg126His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 684,524 control chromosomes in the GnomAD database, including 68,158 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 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. R126L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.53 (18852 hom., cov: 24)
  • Exomes 𝑓: 0.32 (49306 hom.)
• Consequence: KRTAP4-8 NM_031960.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56
• Publications: 7 publications found

Genes affected

KRTAP4-8 (HGNC:17230): (keratin associated protein 4-8) Involved in aging and hair cycle. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0057708025).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031960.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP4-8	NM_031960.3	MANE Select	c.377G>A	p.Arg126His	missense	Exon 1 of 1	NP_114166.1	Q9BYQ9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP4-8	ENST00000333822.5	TSL:6 MANE Select	c.377G>A	p.Arg126His	missense	Exon 1 of 1	ENSP00000328444.4	Q9BYQ9

Frequencies

GnomAD3 genomes AF: 0.531 AC: 65613 AN: 123570 Hom.: 18836 Cov.: 24

Gnomad AFR AF: 0.483

Gnomad AMI AF: 0.582

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.593

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.586

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.580

Gnomad OTH AF: 0.543

GnomAD2 exomes AF: 0.125 AC: 12610 AN: 100516 AF XY: 0.121

Gnomad AFR exome AF: 0.111

Gnomad AMR exome AF: 0.101

Gnomad ASJ exome AF: 0.203

Gnomad EAS exome AF: 0.0358

Gnomad FIN exome AF: 0.232

Gnomad NFE exome AF: 0.137

Gnomad OTH exome AF: 0.180

GnomAD4 exome AF: 0.318 AC: 178437 AN: 560896 Hom.: 49306 Cov.: 25 AF XY: 0.322 AC XY: 92142 AN XY: 285770

African (AFR) AF: 0.246 AC: 3317 AN: 13504

American (AMR) AF: 0.234 AC: 5702 AN: 24388

Ashkenazi Jewish (ASJ) AF: 0.466 AC: 6362 AN: 13640

East Asian (EAS) AF: 0.186 AC: 6158 AN: 33156

South Asian (SAS) AF: 0.294 AC: 13549 AN: 46160

European-Finnish (FIN) AF: 0.519 AC: 16787 AN: 32318

Middle Eastern (MID) AF: 0.438 AC: 937 AN: 2140

European-Non Finnish (NFE) AF: 0.314 AC: 115229 AN: 367396

Other (OTH) AF: 0.369 AC: 10396 AN: 28194

GnomAD4 genome AF: 0.531 AC: 65627 AN: 123628 Hom.: 18852 Cov.: 24 AF XY: 0.527 AC XY: 31804 AN XY: 60330

African (AFR) AF: 0.483 AC: 13791 AN: 28554

American (AMR) AF: 0.492 AC: 6602 AN: 13418

Ashkenazi Jewish (ASJ) AF: 0.593 AC: 1787 AN: 3016

East Asian (EAS) AF: 0.240 AC: 1129 AN: 4710

South Asian (SAS) AF: 0.443 AC: 1846 AN: 4166

European-Finnish (FIN) AF: 0.586 AC: 5107 AN: 8722

Middle Eastern (MID) AF: 0.588 AC: 133 AN: 226

European-Non Finnish (NFE) AF: 0.580 AC: 33821 AN: 58268

Other (OTH) AF: 0.541 AC: 959 AN: 1772

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0491 AC: 4591

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.7
DANN	Benign	0.93
DEOGEN2	Benign	0.064	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.073	T
MetaRNN	Benign	0.0058	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		-1.6
PrimateAI	Benign	0.18	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.065
Sift	Benign	0.070	T
Sift4G	Benign	0.13	T
Polyphen		0.96	D
Vest4		0.053
MPC		0.11
ClinPred		0.060	T
GERP RS		-2.0
PromoterAI		0.0062	Neutral
Varity_R		0.072
gMVP		0.078
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs80168553; hg19: chr17-39253960; COSMIC: COSV61563885; COSMIC: COSV61563885;