17-41190577-C-A

Variant names:

• chr17-41190577-C-A
• rs1040724741
• NM_001190460.1:c.691C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001190460.1(KRTAP9-1):​c.691C>A​(p.Arg231Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 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. R231C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KRTAP9-1 NM_001190460.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.541
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12022525).

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.691C>A	p.Arg231Ser	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.691C>A	p.Arg231Ser	missense	Exon 1 of 1	ENSP00000381488.1	A8MXZ3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	4.3
DANN	Benign	0.80
DEOGEN2	Benign	0.0070	T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.016	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		-0.54
PrimateAI	Benign	0.17	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.021
Sift	Uncertain	0.025	D
Sift4G	Benign	0.28	T
Vest4		0.089
MutPred		0.18		Gain of sheet (P = 0.0827)
MVP		0.088
MPC		0.030
ClinPred		0.15	T
GERP RS		1.3
Varity_R		0.12
gMVP		0.075

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs1040724741; hg19: chr17-39346829;