rs2015329570

Variant names:

• chr17-41190070-T-G
• rs2015329570
• NM_001190460.1:c.184T>G

Variant summary

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

The NM_001190460.1(KRTAP9-1):​c.184T>G​(p.Cys62Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000662 in 151,092 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: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: KRTAP9-1 NM_001190460.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.356

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=0.26541674).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP9-1	NM_001190460.1	c.184T>G	p.Cys62Gly	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.184T>G	p.Cys62Gly	missense_variant	Exon 1 of 1	6	NM_001190460.1	ENSP00000381488.1

Frequencies

GnomAD3 genomes AF: 0.00000662 AC: 1 AN: 151092 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000244

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 102

GnomAD4 genome AF: 0.00000662 AC: 1 AN: 151092 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 73796

Gnomad4 AFR AF: 0.0000244

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 07, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.184T>G (p.C62G) alteration is located in exon 1 (coding exon 1) of the KRTAP9-1 gene. This alteration results from a T to G substitution at nucleotide position 184, causing the cysteine (C) at amino acid position 62 to be replaced by a glycine (G). 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	0.18
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	16
DANN	Benign	0.76
DEOGEN2	Benign	0.11	T;.;.;.
Eigen	Benign	-0.054
Eigen_PC	Benign	-0.19
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.56	T;T;T;T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.27	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.0	M;.;.;.
PrimateAI	Benign	0.22	T
PROVEAN	Pathogenic	-9.2	D;.;.;.
REVEL	Benign	0.11
Sift	Benign	0.060	T;.;.;.
Sift4G	Uncertain	0.016	D;D;D;D
Vest4		0.18
MutPred		0.52		Loss of stability (P = 0.0295);.;.;.;
MVP		0.37
MPC		0.032
ClinPred		0.29	T
GERP RS		2.3
Varity_R		0.37
gMVP		0.47

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: rs2015329570; hg19: chr17-39346322;