rs200119349

Variant names:

• chr17-41190314-G-A
• rs200119349
• NM_001190460.1:c.428G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001190460.1(KRTAP9-1):​c.428G>A​(p.Cys143Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000561 in 1,248,594 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000056 (0 hom.)
• Consequence: KRTAP9-1 NM_001190460.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.23

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27166933).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP9-1	NM_001190460.1	c.428G>A	p.Cys143Tyr	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.428G>A	p.Cys143Tyr	missense_variant	Exon 1 of 1	6	NM_001190460.1	ENSP00000381488.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD3 exomes AF: 0.00000871 AC: 2 AN: 229660 Hom.: 0 AF XY: 0.00000803 AC XY: 1 AN XY: 124514

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000195

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000561 AC: 7 AN: 1248594 Hom.: 0 Cov.: 115 AF XY: 0.00000486 AC XY: 3 AN XY: 616994

Gnomad4 AFR exome AF: 0.00

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: 0.00000615

Gnomad4 OTH exome AF: 0.0000201

GnomAD4 genome Cov.: 0

ExAC AF: 0.00000826 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.428G>A (p.C143Y) alteration is located in exon 1 (coding exon 1) of the KRTAP9-1 gene. This alteration results from a G to A substitution at nucleotide position 428, causing the cysteine (C) at amino acid position 143 to be replaced by a tyrosine (Y). 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	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	15
DANN	Benign	0.52
DEOGEN2	Benign	0.16	T;.;.
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.68	T;T;T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.27	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.0	M;.;.
PrimateAI	Benign	0.28	T
PROVEAN	Pathogenic	-7.1	D;.;.
REVEL	Benign	0.048
Sift	Uncertain	0.0010	D;.;.
Sift4G	Pathogenic	0.0	D;D;D
Vest4		0.16
MutPred		0.43		Gain of relative solvent accessibility (P = 0.1259);.;.;
MVP		0.16
MPC		0.039
ClinPred		0.33	T
GERP RS		1.3
Varity_R		0.44
gMVP		0.18

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: rs200119349; hg19: chr17-39346566;