11-71538524-G-T

Variant names:

• chr11-71538524-G-T
• NM_021046.3:c.469G>T

Variant summary

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

The NM_021046.3(KRTAP5-8):​c.469G>T​(p.Gly157Cys) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: KRTAP5-8 NM_021046.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.549

Genes affected

KRTAP5-8 (HGNC:23603): (keratin associated protein 5-8) 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=0.091180444).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP5-8	NM_021046.3	c.469G>T	p.Gly157Cys	missense_variant	Exon 1 of 1	ENST00000398534.4	NP_066384.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRTAP5-8	ENST00000398534.4	c.469G>T	p.Gly157Cys	missense_variant	Exon 1 of 1	6	NM_021046.3	ENSP00000420723.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.469G>T (p.G157C) alteration is located in exon 1 (coding exon 1) of the KRTAP5-8 gene. This alteration results from a G to T substitution at nucleotide position 469, causing the glycine (G) at amino acid position 157 to be replaced by a cysteine (C). 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	0.12
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	9.8
DANN	Benign	0.78
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.034	T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PROVEAN	Benign	5.9	N
REVEL	Benign	0.12
Sift	Benign	0.20	T
Sift4G	Benign	0.15	T
Polyphen		1.0	D
Vest4		0.17
MutPred		0.22		Loss of glycosylation at S156 (P = 0.0503);
MVP		0.12
MPC		0.046
ClinPred		0.084	T
GERP RS		0.44
Varity_R		0.13
gMVP		0.036

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr11-71249570;