17-41105458-T-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP4-9	NM_001146041.1	c.70T>G	p.Cys24Gly	missense_variant	Exon 1 of 1	ENST00000391415.2	NP_001139513.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRTAP4-9	ENST00000391415.2	c.70T>G	p.Cys24Gly	missense_variant	Exon 1 of 1	6	NM_001146041.1	ENSP00000375234.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 135

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 12, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.70T>G (p.C24G) alteration is located in exon 1 (coding exon 1) of the KRTAP4-9 gene. This alteration results from a T to G substitution at nucleotide position 70, causing the cysteine (C) at amino acid position 24 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.66	D;D
MetaSVM	Benign	-0.56	T
MutationAssessor	Pathogenic	3.7	H;.
PrimateAI	Benign	0.29	T
PROVEAN	Pathogenic	-9.5	D;.
REVEL	Uncertain	0.31
Sift	Benign	0.030	D;.
Sift4G	Uncertain	0.0020	D;D
Polyphen		1.0	D;.
Vest4		0.42
MutPred		0.66		Gain of relative solvent accessibility (P = 0.0104);Gain of relative solvent accessibility (P = 0.0104);
MVP		0.47
MPC		0.22
ClinPred		0.69	D
GERP RS		3.3
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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-39261710;