17-41168163-A-C

Position:

• chr17-41168163-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033187.2(KRTAP4-3):​c.10T>G​(p.Ser4Ala) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KRTAP4-3 NM_033187.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.87

Genes affected

KRTAP4-3 (HGNC:18908): (keratin associated protein 4-3) 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22347245).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP4-3	NM_033187.2	c.10T>G	p.Ser4Ala	missense_variant	1/1	ENST00000391356.4	NP_149443.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTAP4-3	ENST00000391356.4	c.10T>G	p.Ser4Ala	missense_variant	1/1	6	NM_033187.2	ENSP00000375151.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 13, 2023

The c.10T>G (p.S4A) alteration is located in exon 1 (coding exon 1) of the KRTAP4-3 gene. This alteration results from a T to G substitution at nucleotide position 10, causing the serine (S) at amino acid position 4 to be replaced by an alanine (A). 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	0.14
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.060	T
Eigen	Uncertain	0.28
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Pathogenic	3.2	M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.15
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.046	D
Polyphen		0.95	P
Vest4		0.20
MutPred		0.38		Gain of sheet (P = 0.0221);
MVP		0.21
MPC		0.022
ClinPred		0.92	D
GERP RS		4.1
Varity_R		0.26
gMVP		0.058

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

LitVar

Other links and lift over

dbSNP: rs1005585492; hg19: chr17-39324415;