rs764178422

Variant names:

• chr17-41065506-C-G
• rs764178422
• NM_033184.4:c.340G>C

Your query was ambiguous. Multiple possible variants found:

• chr17-41065506-C-G
• chr17-41065506-C-T

Variant summary

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

The NM_033184.4(KRTAP2-4):​c.340G>C​(p.Gly114Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,556,680 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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. G114D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000014 (1 hom.)
• Consequence: KRTAP2-4 NM_033184.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.21
• Publications: 1 publications found

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

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.037301183).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033184.4. 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
	KRTAP2-4	NM_033184.4	MANE Select	c.340G>C	p.Gly114Arg	missense	Exon 1 of 1	NP_149440.1	Q9BYR9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP2-4	ENST00000394015.3	TSL:6 MANE Select	c.340G>C	p.Gly114Arg	missense	Exon 1 of 1	ENSP00000377583.2	Q9BYR9

Frequencies

GnomAD3 genomes AF: 0.0000530 AC: 8 AN: 150906 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000662

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000970

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000297

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000812 AC: 13 AN: 160076 AF XY: 0.0000696

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000941

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000227

GnomAD4 exome AF: 0.0000142 AC: 20 AN: 1405656 Hom.: 1 Cov.: 31 AF XY: 0.0000115 AC XY: 8 AN XY: 694280

African (AFR) AF: 0.00 AC: 0 AN: 32458

American (AMR) AF: 0.00 AC: 0 AN: 36014

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24820

East Asian (EAS) AF: 0.000449 AC: 17 AN: 37834

South Asian (SAS) AF: 0.00 AC: 0 AN: 79532

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46290

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5540

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1084778

Other (OTH) AF: 0.0000514 AC: 3 AN: 58390

GnomAD4 genome AF: 0.0000530 AC: 8 AN: 151024 Hom.: 0 Cov.: 31 AF XY: 0.0000542 AC XY: 4 AN XY: 73814

African (AFR) AF: 0.00 AC: 0 AN: 41364

American (AMR) AF: 0.0000661 AC: 1 AN: 15132

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3456

East Asian (EAS) AF: 0.000972 AC: 5 AN: 5142

South Asian (SAS) AF: 0.00 AC: 0 AN: 4764

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10502

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000297 AC: 2 AN: 67378

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.000124 Hom.: 0

Bravo AF: 0.0000416

ExAC AF: 0.0000357 AC: 4

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	0.16
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0012	T
Eigen	Benign	-0.070
Eigen_PC	Benign	0.043
FATHMM_MKL	Benign	0.53	D
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.037	T
MetaSVM	Benign	-0.85	T
PhyloP100		2.2
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.023
Sift	Benign	0.044	D
Sift4G	Uncertain	0.015	D
Vest4		0.36
MutPred		0.44		Gain of solvent accessibility (P = 0.0263)
MVP		0.27
MPC		1.6
ClinPred		0.22	T
GERP RS		4.5
PromoterAI		-0.0086	Neutral
Varity_R		0.065
gMVP		0.081
Mutation Taster		=84/16	polymorphism

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

Other links and lift over

dbSNP: rs764178422; hg19: chr17-39221758;