chr21-30598804-C-A

Position:

• chr21-30598804-C-A

Variant summary

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

The NM_181604.2(KRTAP6-2):​c.71G>T​(p.Gly24Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: KRTAP6-2 NM_181604.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.87

Genes affected

KRTAP6-2 (HGNC:18932): (keratin associated protein 6-2) Enables identical protein binding activity. Predicted to be involved in keratinization. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP6-2	NM_181604.2	c.71G>T	p.Gly24Val	missense_variant	1/1	ENST00000334897.4	NP_853635.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTAP6-2	ENST00000334897.4	c.71G>T	p.Gly24Val	missense_variant	1/1	6	NM_181604.2	ENSP00000334560.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

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 23, 2023

The c.71G>T (p.G24V) alteration is located in exon 1 (coding exon 1) of the KRTAP6-2 gene. This alteration results from a G to T substitution at nucleotide position 71, causing the glycine (G) at amino acid position 24 to be replaced by a valine (V). 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	0.19
BayesDel_addAF	Benign	-0.059	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	16
DANN	Benign	0.93
DEOGEN2	Benign	0.11	T
Eigen	Benign	0.12
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.84	D
M_CAP	Benign	0.0089	T
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-1.1	T
PROVEAN	Pathogenic	-9.0	D
REVEL	Benign	0.15
Sift4G	Pathogenic	0.0	D
Polyphen		0.79	P
Vest4		0.64
MutPred		0.36		Loss of disorder (P = 0.0099);
MVP		0.26
MPC		0.077
ClinPred		0.74	D
GERP RS		3.5
Varity_R		0.64
gMVP		0.28

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr21-31971123;