rs72625995

chr17-41097583-C-Achr17-41097583-C-Gchr17-41097583-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_031960.3(KRTAP4-8):c.502G>T(p.Ala168Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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. A168T) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KRTAP4-8 NM_031960.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0110

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03894639).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRTAP4-8	NM_031960.3	c.502G>T	p.Ala168Ser	missense_variant	1/1	ENST00000333822.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRTAP4-8	ENST00000333822.5	c.502G>T	p.Ala168Ser	missense_variant	1/1		NM_031960.3	P1

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD3 exomes AF: 0.0000133 AC: 2 AN: 150016 Hom.: 1 AF XY: 0.00 AC XY: 0 AN XY: 78826

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000103

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.13e-7 AC: 1 AN: 1401564 Hom.: 0 Cov.: 96 AF XY: 0.00 AC XY: 0 AN XY: 692524

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000125

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 28

ExAC AF: 0.0000197 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.69
Cadd	Benign	16
Dann	Benign	0.82
DEOGEN2	Benign	0.00046	T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.0060	T;T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.039	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.41	N;.
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	1.1	N;.
REVEL	Benign	0.036
Sift	Benign	0.48	T;.
Sift4G	Benign	0.81	T;T
Polyphen		0.0020	B;.
Vest4		0.077
MutPred		0.30		Gain of glycosylation at A168 (P = 0.0488);.;
MVP		0.014
MPC		0.082
ClinPred		0.043	T
GERP RS		2.6
Varity_R		0.031
gMVP		0.046

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

Publications

LitVar

Other links and lift over

dbSNP: rs72625995; hg19: chr17-39253835;