chr17-41190207-G-T

Variant names:

• chr17-41190207-G-T
• rs542686684
• NM_001190460.1:c.321G>T

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.321G>T​(p.Gln107His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000729 in 1,370,916 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: 34)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: KRTAP9-1 NM_001190460.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.722

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=0.14807793).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP9-1	NM_001190460.1	c.321G>T	p.Gln107His	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.321G>T	p.Gln107His	missense_variant	Exon 1 of 1	6	NM_001190460.1	ENSP00000381488.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD3 exomes AF: 0.00000406 AC: 1 AN: 246550 Hom.: 0 AF XY: 0.00000750 AC XY: 1 AN XY: 133394

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: 0.00000901

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.29e-7 AC: 1 AN: 1370916 Hom.: 0 Cov.: 136 AF XY: 0.00000148 AC XY: 1 AN XY: 677818

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: 9.39e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	8.1
DANN	Benign	0.92
DEOGEN2	Benign	0.010	T;.
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.015	T;T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.8	M;.
PrimateAI	Benign	0.18	T
PROVEAN	Benign	-1.9	N;.
REVEL	Benign	0.043
Sift	Uncertain	0.018	D;.
Sift4G	Uncertain	0.030	D;D
Vest4		0.085
MutPred		0.48		Gain of glycosylation at S112 (P = 0.1163);.;
MVP		0.072
MPC		0.028
ClinPred		0.096	T
GERP RS		0.17
Varity_R		0.11
gMVP		0.083

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs542686684; hg19: chr17-39346459;