11-1621822-C-A

Position:

• chr11-1621822-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001347674.1(KRTAP5-4):​c.272G>T​(p.Cys91Phe) 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. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 21)
• Consequence: KRTAP5-4 NM_001347674.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.57

Genes affected

KRTAP5-4 (HGNC:23599): (keratin associated protein 5-4) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28933287).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP5-4	NM_001347674.1	c.272G>T	p.Cys91Phe	missense_variant	1/1	ENST00000399682.1	NP_001334603.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTAP5-4	ENST00000399682.1	c.272G>T	p.Cys91Phe	missense_variant	1/1		NM_001347674.1	ENSP00000382590	P1

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome Cov.: 56

GnomAD4 genome Cov.: 21

Bravo AF: 0.00000378

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

Nov 09, 2021

The c.452G>T (p.C151F) alteration is located in exon 1 (coding exon 1) of the KRTAP5-4 gene. This alteration results from a G to T substitution at nucleotide position 452, causing the cysteine (C) at amino acid position 151 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
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	17
DANN	Benign	0.83
Eigen	Benign	-0.030
Eigen_PC	Benign	-0.079
FATHMM_MKL	Benign	0.63	D
M_CAP	Benign	0.00096	T
MetaRNN	Benign	0.29	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.99	N
PROVEAN	Uncertain	-3.9	D;.
REVEL	Benign	0.069
Sift	Uncertain	0.021	D;.
Sift4G	Pathogenic	0.0	D;D
Vest4		0.42
MVP		0.088
MPC		0.032
ClinPred		0.21	T
GERP RS		2.5
gMVP		0.016

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: rs1463586225; hg19: chr11-1643052;