17-41097588-C-G

Variant names:

• chr17-41097588-C-G
• rs780974463
• NM_031960.3:c.497G>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.497G>C​(p.Arg166Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000141 in 1,417,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R166H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: KRTAP4-8 NM_031960.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.394
• Publications: 0 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=0.22044557).

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.497G>C	p.Arg166Pro	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.497G>C	p.Arg166Pro	missense	Exon 1 of 1	ENSP00000328444.4	Q9BYQ9

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome AF: 0.00000141 AC: 2 AN: 1417652 Hom.: 0 Cov.: 96 AF XY: 0.00000143 AC XY: 1 AN XY: 700904

African (AFR) AF: 0.00 AC: 0 AN: 31768

American (AMR) AF: 0.00 AC: 0 AN: 38334

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25106

East Asian (EAS) AF: 0.0000265 AC: 1 AN: 37686

South Asian (SAS) AF: 0.0000123 AC: 1 AN: 81558

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5660

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1088260

Other (OTH) AF: 0.00 AC: 0 AN: 58870

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Benign	-0.047	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.079	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.095	N
LIST_S2	Benign	0.16	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Pathogenic	3.9	H
PhyloP100		-0.39
PrimateAI	Benign	0.26	T
PROVEAN	Pathogenic	-5.8	D
REVEL	Benign	0.16
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.021	D
Polyphen		0.064	B
Vest4		0.34
MutPred		0.47		Gain of glycosylation at T163 (P = 0.0362)
MVP		0.12
MPC		0.13
ClinPred		0.79	D
GERP RS		1.5
Varity_R		0.59
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs780974463; hg19: chr17-39253840;