rs749455809

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr17-41315520-C-A
• chr17-41315520-C-T

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>T​(p.Gly44Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000621 in 1,449,832 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: 0.0000062 (0 hom.)
• Consequence: KRTAP17-1 NM_031964.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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=0.30565196).

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>T	p.Gly44Val	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>T	p.Gly44Val	missense	Exon 1 of 1	ENSP00000333993.3	Q9BYP8
	ENSG00000307895	ENST00000829650.1		n.678+15028G>T		intron	N/A
	ENSG00000307895	ENST00000829651.1		n.333-12246G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000177 AC: 4 AN: 225954 AF XY: 0.0000324

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: 0.0000404

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000621 AC: 9 AN: 1449832 Hom.: 0 Cov.: 33 AF XY: 0.00000694 AC XY: 5 AN XY: 720542

African (AFR) AF: 0.00 AC: 0 AN: 33194

American (AMR) AF: 0.00 AC: 0 AN: 43290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25776

East Asian (EAS) AF: 0.00 AC: 0 AN: 39162

South Asian (SAS) AF: 0.00 AC: 0 AN: 85040

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52266

Middle Eastern (MID) AF: 0.000175 AC: 1 AN: 5724

European-Non Finnish (NFE) AF: 0.00000633 AC: 7 AN: 1105564

Other (OTH) AF: 0.0000167 AC: 1 AN: 59816

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000283 Hom.: 0

Bravo AF: 0.00000756

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	0.34
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Benign	19
DANN	Benign	0.78
DEOGEN2	Benign	0.0069	T
Eigen	Benign	0.023
Eigen_PC	Benign	-0.096
FATHMM_MKL	Benign	0.39	N
M_CAP	Benign	0.085	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	1.9	L
PhyloP100		5.6
PrimateAI	Benign	0.35	T
PROVEAN	Benign	3.6	N
REVEL	Uncertain	0.36
Sift4G	Benign	0.13	T
Polyphen		1.0	D
Vest4		0.41
MutPred		0.23		Gain of sheet (P = 0.0101)
MVP		0.58
MPC		0.29
ClinPred		0.22	T
GERP RS		4.0
PromoterAI		0.010	Neutral
Varity_R		0.17
gMVP		0.13
Mutation Taster		=94/6	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: rs749455809; hg19: chr17-39471772;