Genetic Variant NM_031964.2:c.149G>T (chr17-41315502-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_031964.2(KRTAP17-1):c.149G>T(p.Gly50Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 976,752 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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. G50D) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 28)

Exomes 𝑓: 0.0000020 ( 0 hom. )

Consequence

KRTAP17-1
NM_031964.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.61

Publications

0 publications found

Variant links:

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]

KRTAP17-1 links:

ENSG00000307895 (HGNC:):

ENSG00000307895 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.091104).

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>T	p.Gly50Val	missense	Exon 1 of 1	NP_114170.1	Q9BYP8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KRTAP17-1	ENST00000334202.5	TSL:6 MANE Select	c.149G>T	p.Gly50Val	missense	Exon 1 of 1	ENSP00000333993.3	Q9BYP8
ENSG00000307895	ENST00000829650.1		n.678+15046G>T		intron	N/A
ENSG00000307895	ENST00000829651.1		n.333-12228G>T		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

976752

Hom.:

Cov.:

AF XY:

0.00000205

AC XY:

AN XY:

486928

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

18116

American (AMR)

AF:

0.00

AC:

AN:

32714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16836

East Asian (EAS)

AF:

0.00

AC:

AN:

19360

South Asian (SAS)

AF:

0.00

AC:

AN:

60586

European-Finnish (FIN)

AF:

0.0000246

AC:

AN:

40572

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3476

European-Non Finnish (NFE)

AF:

0.00000134

AC:

AN:

746012

Other (OTH)

AF:

0.00

AC:

AN:

39080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

9.2

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.0032

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.033

M_CAP

Benign

0.0077

MetaRNN

Benign

0.091

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

PhyloP100

-1.6

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.3

REVEL

Benign

0.031

Sift4G

Uncertain

0.021

Polyphen

0.40

Vest4

0.35

MutPred

0.25

Gain of sheet (P = 0.0043)

MVP

0.082

MPC

0.29

ClinPred

0.092

GERP RS

1.9

PromoterAI

0.012

Neutral

(source)

Varity_R

0.18

gMVP

0.049

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over