21-30592469-G-T

Position:

• chr21-30592469-G-T

Variant summary

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

The NM_181605.4(KRTAP6-3):​c.24G>T​(p.Met8Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 9/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KRTAP6-3 NM_181605.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.12

Genes affected

KRTAP6-3 (HGNC:18933): (keratin associated protein 6-3) 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
KRTAP6-3	NM_181605.4	c.24G>T	p.Met8Ile	missense_variant	1/1	ENST00000391624.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTAP6-3	ENST00000391624.1	c.24G>T	p.Met8Ile	missense_variant	1/1	6	NM_181605.4	ENSP00000375482.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Oct 05, 2022

The c.24G>T (p.M8I) alteration is located in exon 1 (coding exon 1) of the KRTAP6-3 gene. This alteration results from a G to T substitution at nucleotide position 24, causing the methionine (M) at amino acid position 8 to be replaced by an isoleucine (I). 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	-0.0015	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	19
DANN	Benign	0.95
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.86	D
M_CAP	Benign	0.042	D
MetaRNN	Uncertain	0.53	D
MetaSVM	Benign	-0.91	T
REVEL	Benign	0.28
Sift4G	Benign	0.086	T
Vest4		0.55
MVP		0.082
ClinPred		0.51	D
GERP RS		4.4
gMVP		0.097

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr21-31964788;