17-41009055-C-T

Variant names:

• chr17-41009055-C-T
• rs141325742
• NM_031958.2:c.20G>A

Variant summary

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

The NM_031958.2(KRTAP3-1):​c.20G>A​(p.Arg7His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000824 in 1,613,632 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R7C) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00029 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000061 (0 hom.)
• Consequence: KRTAP3-1 NM_031958.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.804
• Publications: 4 publications found

Genes affected

KRTAP3-1 (HGNC:16778): (keratin associated protein 3-1) 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]

ENSG00000306126 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.053782582).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031958.2. 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
	KRTAP3-1	NM_031958.2	MANE Select	c.20G>A	p.Arg7His	missense	Exon 1 of 1	NP_114164.1	Q9BYR8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP3-1	ENST00000391588.3	TSL:6 MANE Select	c.20G>A	p.Arg7His	missense	Exon 1 of 1	ENSP00000375430.1	Q9BYR8
	KRTAP3-1	ENST00000581033.1	TSL:3	n.132-10G>A		intron	N/A
	ENSG00000306126	ENST00000815517.1		n.219+28448C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000289 AC: 44 AN: 152006 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000846

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000328

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000959

GnomAD2 exomes AF: 0.0000843 AC: 21 AN: 249252 AF XY: 0.0000594

Gnomad AFR exome AF: 0.000742

Gnomad AMR exome AF: 0.0000869

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000357

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000609 AC: 89 AN: 1461626 Hom.: 0 Cov.: 32 AF XY: 0.0000495 AC XY: 36 AN XY: 727098

African (AFR) AF: 0.000747 AC: 25 AN: 33480

American (AMR) AF: 0.000224 AC: 10 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26088

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86214

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000414 AC: 46 AN: 1111880

Other (OTH) AF: 0.0000662 AC: 4 AN: 60392

GnomAD4 genome AF: 0.000289 AC: 44 AN: 152006 Hom.: 0 Cov.: 32 AF XY: 0.000242 AC XY: 18 AN XY: 74246

African (AFR) AF: 0.000846 AC: 35 AN: 41386

American (AMR) AF: 0.000328 AC: 5 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67982

Other (OTH) AF: 0.000959 AC: 2 AN: 2086

Alfa AF: 0.000246 Hom.: 0

Bravo AF: 0.000261

ESP6500AA AF: 0.00136 AC: 6

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000115 AC: 14

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	15
DANN	Benign	0.82
DEOGEN2	Benign	0.042	T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.12	N
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.80
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.067
Sift	Benign	0.10	T
Sift4G	Benign	0.42	T
Polyphen		0.81	P
Vest4		0.36
MVP		0.17
MPC		0.035
ClinPred		0.024	T
GERP RS		4.8
PromoterAI		0.0053	Neutral
Varity_R		0.11
gMVP		0.094
Mutation Taster		=93/7	polymorphism

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: rs141325742; hg19: chr17-39165307; COSMIC: COSV66957433; COSMIC: COSV66957433;