chr17-41315502-C-T

Variant names:

• chr17-41315502-C-T
• rs2017047836
• NM_031964.2:c.149G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_031964.2(KRTAP17-1):​c.149G>A​(p.Gly50Asp) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 28)
• Consequence: KRTAP17-1 NM_031964.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.61
• Publications: 0 publications found

Genes affected

KRTAP17-1 (HGNC:18917): (keratin associated protein 17-1) This protein is a member of the keratin-associated protein (KAP) family. The KAP proteins form a matrix of keratin intermediate filaments which contribute to the structure of hair fibers. KAP family members appear to have unique, family-specific amino- and carboxyl-terminal regions and are subdivided into three multi-gene families according to amino acid composition: the high sulfur, the ultrahigh sulfur, and the high tyrosine/glycine KAPs. This protein is a member of the ultrahigh sulfur KAP family and the gene is localized to a cluster of KAPs at 17q12-q21. [provided by RefSeq, Jul 2008]

ENSG00000307895 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.056953102).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031964.2. 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
	KRTAP17-1	NM_031964.2	MANE Select	c.149G>A	p.Gly50Asp	missense	Exon 1 of 1	NP_114170.1	Q9BYP8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP17-1	ENST00000334202.5	TSL:6 MANE Select	c.149G>A	p.Gly50Asp	missense	Exon 1 of 1	ENSP00000333993.3	Q9BYP8
	ENSG00000307895	ENST00000829650.1		n.678+15046G>A		intron	N/A
	ENSG00000307895	ENST00000829651.1		n.333-12228G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 28

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	Uncertain	0.37
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	6.1
DANN	Benign	0.86
DEOGEN2	Benign	0.0042	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.023	N
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		-1.6
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.50	N
REVEL	Benign	0.084
Sift4G	Benign	0.063	T
Polyphen		0.0020	B
Vest4		0.23
MutPred		0.17		Gain of loop (P = 0.0851)
MVP		0.043
MPC		0.30
ClinPred		0.042	T
GERP RS		1.9
PromoterAI		0.0014	Neutral
Varity_R		0.13
gMVP		0.051

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs2017047836; hg19: chr17-39471754;