17-41097558-C-T

Variant names:

• chr17-41097558-C-T
• rs777688954
• NM_031960.3:c.527G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_031960.3(KRTAP4-8):​c.527G>A​(p.Arg176His) variant causes a missense change. The variant allele was found at a frequency of 0.0000438 in 1,416,958 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000044 (0 hom.)
• Consequence: KRTAP4-8 NM_031960.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.86
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32042313).

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.527G>A	p.Arg176His	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.527G>A	p.Arg176His	missense	Exon 1 of 1	ENSP00000328444.4	Q9BYQ9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000168 AC: 3 AN: 178450 AF XY: 0.0000318

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000136

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000438 AC: 62 AN: 1416958 Hom.: 0 Cov.: 88 AF XY: 0.0000500 AC XY: 35 AN XY: 700526

African (AFR) AF: 0.0000319 AC: 1 AN: 31380

American (AMR) AF: 0.00 AC: 0 AN: 37906

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25234

East Asian (EAS) AF: 0.00 AC: 0 AN: 37388

South Asian (SAS) AF: 0.0000738 AC: 6 AN: 81284

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50512

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.0000487 AC: 53 AN: 1088692

Other (OTH) AF: 0.0000340 AC: 2 AN: 58864

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000286 Hom.: 0

ExAC AF: 0.0000435 AC: 5

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	0.15
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.053	T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		3.9
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.094
Sift	Uncertain	0.029	D
Sift4G	Benign	0.12	T
Polyphen		1.0	D
Vest4		0.32
MVP		0.19
MPC		0.11
ClinPred		0.81	D
GERP RS		2.7
Varity_R		0.14
gMVP		0.11
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs777688954; hg19: chr17-39253810;