17-41315520-C-T

Variant names:

• chr17-41315520-C-T
• rs749455809
• NM_031964.2:c.131G>A

Variant summary

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

The NM_031964.2(KRTAP17-1):​c.131G>A​(p.Gly44Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. G44V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KRTAP17-1 NM_031964.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.63
• 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: 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=0.38283086).

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.131G>A	p.Gly44Glu	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.131G>A	p.Gly44Glu	missense	Exon 1 of 1	ENSP00000333993.3	Q9BYP8
	ENSG00000307895	ENST00000829650.1		n.678+15028G>A		intron	N/A
	ENSG00000307895	ENST00000829651.1		n.333-12246G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000828 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.70
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Benign	20
DANN	Benign	0.56
DEOGEN2	Benign	0.0068	T
Eigen	Benign	0.023
Eigen_PC	Benign	-0.096
FATHMM_MKL	Benign	0.36	N
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		5.6
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.25	N
REVEL	Uncertain	0.32
Sift4G	Uncertain	0.058	T
Polyphen		1.0	D
Vest4		0.46
MutPred		0.20		Gain of sheet (P = 0.0477)
MVP		0.55
MPC		0.30
ClinPred		0.38	T
GERP RS		4.0
PromoterAI		0.0026	Neutral
Varity_R		0.15
gMVP		0.10

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: rs749455809; hg19: chr17-39471772; COSMIC: COSV100498578;