17-41190623-A-G

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001190460.1(KRTAP9-1):​c.737A>G​(p.Gln246Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,442,736 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.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: KRTAP9-1 NM_001190460.1 missense
• Clinical Significance: Not reported in ClinVar
• 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04899794).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP9-1	NM_001190460.1	c.737A>G	p.Gln246Arg	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>G	p.Gln246Arg	missense_variant	Exon 1 of 1	6	NM_001190460.1	ENSP00000381488.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.93e-7 AC: 1 AN: 1442736 Hom.: 0 Cov.: 37 AF XY: 0.00000140 AC XY: 1 AN XY: 715672

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: 9.07e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.0
DANN	Benign	0.87
DEOGEN2	Benign	0.0012	T;.
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.0099	T;T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.049	T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.96	L;.
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.88	N;.
REVEL	Benign	0.049
Sift	Benign	1.0	T;.
Sift4G	Benign	0.49	T;T
Vest4		0.083
MutPred		0.19		Gain of phosphorylation at S248 (P = 0.0626);.;
MVP		0.095
MPC		0.030
ClinPred		0.037	T
GERP RS		-3.1
Varity_R		0.084
gMVP		0.038

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-39346875;