NM_001146041.1:c.70T>G

Variant names:

• chr17-41105458-T-G
• rs2014065127
• NM_001146041.1:c.70T>G

Variant summary

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

The NM_001146041.1(KRTAP4-9):​c.70T>G​(p.Cys24Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: KRTAP4-9 NM_001146041.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.49
• Publications: 0 publications found

Genes affected

KRTAP4-9 (HGNC:18910): (keratin associated protein 4-9) Involved in aging and hair cycle. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001146041.1. 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
	KRTAP4-9	NM_001146041.1	MANE Select	c.70T>G	p.Cys24Gly	missense	Exon 1 of 1	NP_001139513.1	Q9BYQ8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP4-9	ENST00000391415.2	TSL:6 MANE Select	c.70T>G	p.Cys24Gly	missense	Exon 1 of 1	ENSP00000375234.1	Q9BYQ8

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 135

GnomAD4 genome Cov.: 30

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Uncertain	0.083	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	21
DANN	Benign	0.92
DEOGEN2	Benign	0.091	T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.66	D
MetaSVM	Benign	-0.56	T
MutationAssessor	Pathogenic	3.7	H
PhyloP100		1.5
PrimateAI	Benign	0.29	T
PROVEAN	Pathogenic	-9.5	D
REVEL	Uncertain	0.31
Sift	Benign	0.030	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.42
MutPred		0.66		Gain of relative solvent accessibility (P = 0.0104)
MVP		0.47
MPC		0.22
ClinPred		0.69	D
GERP RS		3.3
PromoterAI		-0.0054	Neutral
Varity_R		0.94
gMVP		0.093

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

Other links and lift over

dbSNP: rs2014065127; hg19: chr17-39261710;