21-30371859-A-T

Position:

• chr21-30371859-A-T

Variant summary

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

The NM_181621.4(KRTAP13-2):​c.355T>A​(p.Ser119Thr) 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. 14/21 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: KRTAP13-2 NM_181621.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.497

Genes affected

KRTAP13-2 (HGNC:18923): (keratin associated protein 13-2) 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=0.08741763).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP13-2	NM_181621.4	c.355T>A	p.Ser119Thr	missense_variant	1/1	ENST00000399889.4	NP_853652.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTAP13-2	ENST00000399889.4	c.355T>A	p.Ser119Thr	missense_variant	1/1	6	NM_181621.4	ENSP00000382777.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

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

Feb 05, 2024

The c.355T>A (p.S119T) alteration is located in exon 1 (coding exon 1) of the KRTAP13-2 gene. This alteration results from a T to A substitution at nucleotide position 355, causing the serine (S) at amino acid position 119 to be replaced by a threonine (T). 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	0.10
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	9.0
DANN	Benign	0.93
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.087	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Pathogenic	3.0	M
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.10
Sift	Benign	0.19	T
Sift4G	Benign	0.33	T
Polyphen		0.48	P
Vest4		0.12
MutPred		0.43		Gain of relative solvent accessibility (P = 0.0479);
MVP		0.13
MPC		0.075
ClinPred		0.30	T
GERP RS		-0.79
Varity_R		0.15
gMVP		0.026

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: chr21-31744177;