chr17-41097544-C-T

Variant names:

• chr17-41097544-C-T
• rs371762497
• NM_031960.3:c.541G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_031960.3(KRTAP4-8):​c.541G>A​(p.Ala181Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000875 in 1,566,202 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00029 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000066 (2 hom.)
• Consequence: KRTAP4-8 NM_031960.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.355
• Publications: 1 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.01485455).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

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.541G>A	p.Ala181Thr	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.541G>A	p.Ala181Thr	missense	Exon 1 of 1	ENSP00000328444.4	Q9BYQ9

Frequencies

GnomAD3 genomes AF: 0.000290 AC: 44 AN: 151950 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000776

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.000480

GnomAD2 exomes AF: 0.0000629 AC: 11 AN: 174864 AF XY: 0.0000759

Gnomad AFR exome AF: 0.000507

Gnomad AMR exome AF: 0.0000382

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000561

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000658 AC: 93 AN: 1414252 Hom.: 2 Cov.: 88 AF XY: 0.0000701 AC XY: 49 AN XY: 698902

African (AFR) AF: 0.00108 AC: 34 AN: 31480

American (AMR) AF: 0.0000268 AC: 1 AN: 37318

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25196

East Asian (EAS) AF: 0.00 AC: 0 AN: 37088

South Asian (SAS) AF: 0.0000619 AC: 5 AN: 80776

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50460

Middle Eastern (MID) AF: 0.000350 AC: 2 AN: 5708

European-Non Finnish (NFE) AF: 0.0000349 AC: 38 AN: 1087420

Other (OTH) AF: 0.000221 AC: 13 AN: 58806

GnomAD4 genome AF: 0.000290 AC: 44 AN: 151950 Hom.: 0 Cov.: 32 AF XY: 0.000229 AC XY: 17 AN XY: 74216

African (AFR) AF: 0.000776 AC: 32 AN: 41246

American (AMR) AF: 0.000131 AC: 2 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

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

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68032

Other (OTH) AF: 0.000480 AC: 1 AN: 2084

Alfa AF: 0.0000851 Hom.: 0

Bravo AF: 0.000234

ESP6500AA AF: 0.000723 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000111 AC: 13

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	0.093
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	8.5
DANN	Benign	0.85
DEOGEN2	Benign	0.0061	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.019	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.015	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		-0.35
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.061
Sift	Benign	0.41	T
Sift4G	Benign	0.58	T
Polyphen		0.024	B
Vest4		0.074
MVP		0.014
MPC		0.087
ClinPred		0.013	T
GERP RS		-0.99
Varity_R		0.035
gMVP		0.043
Mutation Taster		=100/0	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: rs371762497; hg19: chr17-39253796; COSMIC: COSV61565891; COSMIC: COSV61565891;