rs781727710

Variant names:

• chr17-41097699-C-A
• rs781727710
• NM_031960.3:c.386G>T

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.386G>T​(p.Cys129Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000587 in 1,362,114 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 27)
  • Exomes 𝑓: 0.0000059 (0 hom.)
• Consequence: KRTAP4-8 NM_031960.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.55
• 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=0.22384515).

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.386G>T	p.Cys129Phe	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.386G>T	p.Cys129Phe	missense	Exon 1 of 1	ENSP00000328444.4	Q9BYQ9

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD2 exomes AF: 0.0000305 AC: 6 AN: 196780 AF XY: 0.0000470

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000355

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000587 AC: 8 AN: 1362114 Hom.: 0 Cov.: 88 AF XY: 0.00000888 AC XY: 6 AN XY: 675418

African (AFR) AF: 0.00 AC: 0 AN: 31736

American (AMR) AF: 0.00 AC: 0 AN: 38670

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23946

East Asian (EAS) AF: 0.000180 AC: 7 AN: 38796

South Asian (SAS) AF: 0.00 AC: 0 AN: 80106

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49950

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4348

European-Non Finnish (NFE) AF: 9.63e-7 AC: 1 AN: 1037936

Other (OTH) AF: 0.00 AC: 0 AN: 56626

GnomAD4 genome Cov.: 27

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.0000395 AC: 4

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	0.14
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.24	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	4.0	H
PhyloP100		1.5
PrimateAI	Benign	0.24	T
PROVEAN	Pathogenic	-7.8	D
REVEL	Benign	0.14
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.98	D
Vest4		0.36
MutPred		0.40		Gain of sheet (P = 0.0477)
MVP		0.23
MPC		0.14
ClinPred		0.59	D
GERP RS		3.7
PromoterAI		-0.0014	Neutral
Varity_R		0.84
gMVP		0.16
Mutation Taster		=96/4	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: rs781727710; hg19: chr17-39253951;