17-41097583-C-G

Variant names:

• chr17-41097583-C-G
• rs72625995
• NM_031960.3:c.502G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031960.3(KRTAP4-8):​c.502G>C​(p.Ala168Pro) 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. 15/22 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KRTAP4-8 NM_031960.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0110
• Publications: 15 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12253913).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP4-8	NM_031960.3	c.502G>C	p.Ala168Pro	missense_variant	Exon 1 of 1	ENST00000333822.5	NP_114166.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRTAP4-8	ENST00000333822.5	c.502G>C	p.Ala168Pro	missense_variant	Exon 1 of 1	6	NM_031960.3	ENSP00000328444.4

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1401564 Hom.: 0 Cov.: 96 AF XY: 0.00 AC XY: 0 AN XY: 692524

African (AFR) AF: 0.00 AC: 0 AN: 26574

American (AMR) AF: 0.00 AC: 0 AN: 37222

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24828

East Asian (EAS) AF: 0.00 AC: 0 AN: 37366

South Asian (SAS) AF: 0.00 AC: 0 AN: 80008

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49936

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5624

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1082178

Other (OTH) AF: 0.00 AC: 0 AN: 57828

GnomAD4 genome Cov.: 28

Alfa AF: 0.00 Hom.: 5162

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0076	T;.
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.047	T;T
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.64	N;.
PhyloP100		-0.011
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.1	N;.
REVEL	Benign	0.066
Sift	Benign	0.047	D;.
Sift4G	Benign	0.12	T;T
Polyphen		0.044	B;.
Vest4		0.25
MutPred		0.44		Gain of catalytic residue at P167 (P = 0.0112);.;
MVP		0.055
MPC		0.12
ClinPred		0.37	T
GERP RS		2.6
Varity_R		0.15
gMVP		0.068

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs72625995; hg19: chr17-39253835;