17-41226679-T-A

Variant names:

• chr17-41226679-T-A
• rs758499842
• NM_031961.3:c.25T>A

Variant summary

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

The NM_031961.3(KRTAP9-2):​c.25T>A​(p.Cys9Ser) 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. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 36)
• Consequence: KRTAP9-2 NM_031961.3 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 2.89
• Publications: 0 publications found

Genes affected

KRTAP9-2 (HGNC:16926): (keratin associated protein 9-2) 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]

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=0.27373558).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031961.3. 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
	KRTAP9-2	NM_031961.3	MANE Select	c.25T>A	p.Cys9Ser	missense	Exon 1 of 1	NP_114167.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP9-2	ENST00000377721.3	TSL:6 MANE Select	c.25T>A	p.Cys9Ser	missense	Exon 1 of 1	ENSP00000366950.3	Q9BYQ4

Frequencies

GnomAD3 genomes Cov.: 36

GnomAD4 exome Cov.: 163

GnomAD4 genome Cov.: 36

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	High myopia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.054	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	20
DANN	Benign	0.94
DEOGEN2	Benign	0.083	T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		2.9
PrimateAI	Benign	0.29	T
PROVEAN	Pathogenic	-8.8	D
REVEL	Benign	0.11
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.010	D
Polyphen		0.90	P
Vest4		0.20
MutPred		0.41		Gain of glycosylation at C9 (P = 0.0155)
MVP		0.25
MPC		1.4
ClinPred		0.92	D
GERP RS		3.1
PromoterAI		-0.0024	Neutral
Varity_R		0.63
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs758499842; hg19: chr17-39382931;