rs1598022287

Variant names:

• chr17-41190623-A-C
• rs1598022287
• NM_001190460.1:c.737A>C

Your query was ambiguous. Multiple possible variants found:

• chr17-41190623-A-C
• chr17-41190623-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001190460.1(KRTAP9-1):​c.737A>C​(p.Gln246Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000277 in 1,442,734 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: KRTAP9-1 NM_001190460.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.984

Genes affected

KRTAP9-1 (HGNC:18912): (keratin associated protein 9-1) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12154117).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP9-1	NM_001190460.1	c.737A>C	p.Gln246Pro	missense_variant	Exon 1 of 1	ENST00000398470.1	NP_001177389.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRTAP9-1	ENST00000398470.1	c.737A>C	p.Gln246Pro	missense_variant	Exon 1 of 1	6	NM_001190460.1	ENSP00000381488.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000277 AC: 4 AN: 1442734 Hom.: 0 Cov.: 37 AF XY: 0.00000140 AC XY: 1 AN XY: 715672

Gnomad4 AFR exome AF: 0.000121

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 25, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.737A>C (p.Q246P) alteration is located in exon 1 (coding exon 1) of the KRTAP9-1 gene. This alteration results from a A to C substitution at nucleotide position 737, causing the glutamine (Q) at amino acid position 246 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	5.9
DANN	Benign	0.90
DEOGEN2	Benign	0.0041	T;.
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.010	T;T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Pathogenic	3.1	M;.
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-2.3	N;.
REVEL	Benign	0.074
Sift	Uncertain	0.021	D;.
Sift4G	Uncertain	0.057	T;T
Vest4		0.21
MutPred		0.24		Gain of glycosylation at S248 (P = 0.0525);.;
MVP		0.092
MPC		0.032
ClinPred		0.17	T
GERP RS		-3.1
Varity_R		0.31
gMVP		0.091

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

Publications

LitVar

Other links and lift over

dbSNP: rs1598022287; hg19: chr17-39346875; COSMIC: COSV59166599; COSMIC: COSV59166599;