11-1608124-C-G

Position:

• chr11-1608124-C-G

Variant summary

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

The NM_001012708.2(KRTAP5-3):​c.262G>C​(p.Gly88Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,455,406 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: KRTAP5-3 NM_001012708.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.00

Genes affected

KRTAP5-3 (HGNC:23598): (keratin associated protein 5-3) 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=0.13153946).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP5-3	NM_001012708.2	c.262G>C	p.Gly88Arg	missense_variant	1/1	ENST00000399685.1	NP_001012726.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTAP5-3	ENST00000399685.1	c.262G>C	p.Gly88Arg	missense_variant	1/1	6	NM_001012708.2	ENSP00000382592.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1455406 Hom.: 0 Cov.: 100 AF XY: 0.00000276 AC XY: 2 AN XY: 723970

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000507

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.02e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

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

Feb 13, 2024

The c.262G>C (p.G88R) alteration is located in exon 1 (coding exon 1) of the KRTAP5-3 gene. This alteration results from a G to C substitution at nucleotide position 262, causing the glycine (G) at amino acid position 88 to be replaced by an arginine (R). 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	0.24
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	6.3
DANN	Benign	0.90
DEOGEN2	Benign	0.033	T
Eigen	Benign	-0.045
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.095	N
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.7	M
PROVEAN	Benign	1.2	N
REVEL	Benign	0.089
Sift	Benign	0.47	T
Sift4G	Benign	0.32	T
Polyphen		1.0	D
Vest4		0.18
MutPred		0.27		Loss of ubiquitination at K84 (P = 0.0301);
MVP		0.030
MPC		0.022
ClinPred		0.24	T
GERP RS		3.0
Varity_R		0.029
gMVP		0.013

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: rs1413395413; hg19: chr11-1629354;