21-30425792-A-G

Position:

• chr21-30425792-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_181622.2(KRTAP13-3):​c.121T>C​(p.Cys41Arg) 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 pathogenic outcome for this variant. 13/21 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: 1.03

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.906

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP13-3	NM_181622.2	c.121T>C	p.Cys41Arg	missense_variant	1/1	ENST00000390690.3	NP_853653.1
LOC105372772	XR_937653.3	n.196-32432T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTAP13-3	ENST00000390690.3	c.121T>C	p.Cys41Arg	missense_variant	1/1	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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 16, 2024

The c.121T>C (p.C41R) alteration is located in exon 1 (coding exon 1) of the KRTAP13-3 gene. This alteration results from a T to C substitution at nucleotide position 121, causing the cysteine (C) at amino acid position 41 to be replaced by an arginine (R). 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	0.17
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	19
DANN	Benign	0.75
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0045	T
MetaRNN	Pathogenic	0.91	D
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.9	L
PrimateAI	Benign	0.39	T
PROVEAN	Pathogenic	-6.5	D
REVEL	Benign	0.26
Sift	Benign	0.15	T
Sift4G	Benign	0.12	T
Polyphen		0.17	B
Vest4		0.59
MutPred		0.84		Gain of phosphorylation at S44 (P = 0.0559);
MVP		0.085
MPC		0.013
ClinPred		0.26	T
GERP RS		3.6
Varity_R		0.46
gMVP		0.15

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: chr21-31798110;