NM_001190460.1:c.344G>C

Variant names:

• chr17-41190230-G-C
• rs749017430
• NM_001190460.1:c.344G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001190460.1(KRTAP9-1):​c.344G>C​(p.Cys115Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000801 in 1,248,376 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C115Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 8.0e-7 (0 hom.)
• Consequence: KRTAP9-1 NM_001190460.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.218
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32085907).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001190460.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP9-1	NM_001190460.1	MANE Select	c.344G>C	p.Cys115Ser	missense	Exon 1 of 1	NP_001177389.1	A8MXZ3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP9-1	ENST00000398470.1	TSL:6 MANE Select	c.344G>C	p.Cys115Ser	missense	Exon 1 of 1	ENSP00000381488.1	A8MXZ3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 8.01e-7 AC: 1 AN: 1248376 Hom.: 0 Cov.: 134 AF XY: 0.00000162 AC XY: 1 AN XY: 616154

African (AFR) AF: 0.00 AC: 0 AN: 26822

American (AMR) AF: 0.00 AC: 0 AN: 28464

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20200

East Asian (EAS) AF: 0.00 AC: 0 AN: 28890

South Asian (SAS) AF: 0.0000155 AC: 1 AN: 64318

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45122

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5030

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 979830

Other (OTH) AF: 0.00 AC: 0 AN: 49700

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	15
DANN	Benign	0.63
DEOGEN2	Benign	0.061	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		0.22
PrimateAI	Benign	0.25	T
PROVEAN	Uncertain	-4.2	D
REVEL	Benign	0.10
Sift	Benign	0.20	T
Sift4G	Uncertain	0.027	D
Vest4		0.20
MutPred		0.72		Gain of relative solvent accessibility (P = 0.0479)
MVP		0.14
MPC		0.032
ClinPred		0.27	T
GERP RS		1.5
PromoterAI		0.0044	Neutral
Varity_R		0.15
gMVP		0.099

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs749017430; hg19: chr17-39346482;