17-41315502-C-G

Variant names:

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

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>C​(p.Gly50Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000279 in 1,074,024 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: 𝑓 0.000010 (0 hom., cov: 28)
  • Exomes 𝑓: 0.0000020 (0 hom.)
• Consequence: KRTAP17-1 NM_031964.2 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.06333688).

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>C	p.Gly50Ala	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>C	p.Gly50Ala	missense	Exon 1 of 1	ENSP00000333993.3	Q9BYP8
	ENSG00000307895	ENST00000829650.1		n.678+15046G>C		intron	N/A
	ENSG00000307895	ENST00000829651.1		n.333-12228G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000103 AC: 1 AN: 97272 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000302

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 2 AN: 976752 Hom.: 0 Cov.: 28 AF XY: 0.00000411 AC XY: 2 AN XY: 486928

African (AFR) AF: 0.00 AC: 0 AN: 18116

American (AMR) AF: 0.00 AC: 0 AN: 32714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16836

East Asian (EAS) AF: 0.00 AC: 0 AN: 19360

South Asian (SAS) AF: 0.0000330 AC: 2 AN: 60586

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40572

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3476

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 746012

Other (OTH) AF: 0.00 AC: 0 AN: 39080

GnomAD4 genome AF: 0.0000103 AC: 1 AN: 97272 Hom.: 0 Cov.: 28 AF XY: 0.0000208 AC XY: 1 AN XY: 48030

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 22174

American (AMR) AF: 0.00 AC: 0 AN: 10608

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2238

East Asian (EAS) AF: 0.00 AC: 0 AN: 2488

South Asian (SAS) AF: 0.000302 AC: 1 AN: 3316

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8536

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 176

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 45618

Other (OTH) AF: 0.00 AC: 0 AN: 1316

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	4.2
DANN	Benign	0.85
DEOGEN2	Benign	0.0040	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.026	N
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		-1.6
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.13	N
REVEL	Benign	0.041
Sift4G	Benign	0.070	T
Polyphen		0.12	B
Vest4		0.20
MutPred		0.16		Gain of sheet (P = 0.0344)
MVP		0.068
MPC		0.25
ClinPred		0.080	T
GERP RS		1.9
PromoterAI		-0.011	Neutral
Varity_R		0.14
gMVP		0.047

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;