17-41105888-C-T

Position:

• chr17-41105888-C-T

Variant summary

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

The NM_001146041.1(KRTAP4-9):​c.500C>T​(p.Ser167Phe) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KRTAP4-9 NM_001146041.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.224

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22035977).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP4-9	NM_001146041.1	c.500C>T	p.Ser167Phe	missense_variant	1/1	ENST00000391415.2	NP_001139513.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTAP4-9	ENST00000391415.2	c.500C>T	p.Ser167Phe	missense_variant	1/1	6	NM_001146041.1	ENSP00000375234.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

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

Sep 04, 2024

The c.500C>T (p.S167F) alteration is located in exon 1 (coding exon 1) of the KRTAP4-9 gene. This alteration results from a C to T substitution at nucleotide position 500, causing the serine (S) at amino acid position 167 to be replaced by a phenylalanine (F). 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	0.28
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T;.
Eigen	Benign	-0.012
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.16	N
LIST_S2	Uncertain	0.94	D;T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Pathogenic	4.1	H;.
PrimateAI	Benign	0.25	T
PROVEAN	Uncertain	-4.1	D;.
REVEL	Benign	0.076
Sift	Uncertain	0.0050	D;.
Sift4G	Uncertain	0.0020	D;D
Polyphen		0.98	D;.
Vest4		0.26
MutPred		0.27		Loss of relative solvent accessibility (P = 0.0071);.;
MVP		0.36
MPC		0.20
ClinPred		0.71	D
GERP RS		2.7
Varity_R		0.18
gMVP		0.039

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

Publications

LitVar

Other links and lift over

dbSNP: rs867033456; hg19: chr17-39262140;