chr21-30425870-G-A

Variant names:

• chr21-30425870-G-A
• NM_181622.2:c.43C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_181622.2(KRTAP13-3):​c.43C>T​(p.His15Tyr) 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. 15/21 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: KRTAP13-3 NM_181622.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.578

Genes affected

KRTAP13-3 (HGNC:18925): (keratin associated protein 13-3) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

LOC105372772 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05172828).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP13-3	NM_181622.2	c.43C>T	p.His15Tyr	missense_variant	Exon 1 of 1	ENST00000390690.3	NP_853653.1
LOC105372772	XR_937653.3	n.196-32510C>T		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRTAP13-3	ENST00000390690.3	c.43C>T	p.His15Tyr	missense_variant	Exon 1 of 1	6	NM_181622.2	ENSP00000375109.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 09, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.43C>T (p.H15Y) alteration is located in exon 1 (coding exon 1) of the KRTAP13-3 gene. This alteration results from a C to T substitution at nucleotide position 43, causing the histidine (H) at amino acid position 15 to be replaced by a tyrosine (Y). 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	0.060
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.057
DANN	Benign	0.38
DEOGEN2	Benign	0.016	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0092	N
LIST_S2	Benign	0.031	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-0.97	N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	1.8	N
REVEL	Benign	0.0050
Sift	Benign	0.24	T
Sift4G	Benign	0.78	T
Polyphen		0.0010	B
Vest4		0.20
MutPred		0.33		Loss of sheet (P = 0.1398);
MVP		0.030
MPC		0.0090
ClinPred		0.12	T
GERP RS		-3.8
Varity_R		0.034
gMVP		0.034

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: chr21-31798188;