21-30425455-G-A

Position:

• chr21-30425455-G-A

Variant summary

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

The NM_181622.2(KRTAP13-3):​c.458C>T​(p.Pro153Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,884 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: KRTAP13-3 NM_181622.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.76

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09869602).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP13-3	NM_181622.2	c.458C>T	p.Pro153Leu	missense_variant	1/1	ENST00000390690.3	NP_853653.1
LOC105372772	XR_937653.3	n.196-32095C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTAP13-3	ENST00000390690.3	c.458C>T	p.Pro153Leu	missense_variant	1/1	6	NM_181622.2	ENSP00000375109.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455884 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 723622

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.02e-7

Gnomad4 OTH exome AF: 0.00

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

Aug 19, 2023

The c.458C>T (p.P153L) 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 458, causing the proline (P) at amino acid position 153 to be replaced by a leucine (L). 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	0.14
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	11
DANN	Benign	0.56
DEOGEN2	Benign	0.025	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.050	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.099	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.73	N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.45	N
REVEL	Benign	0.068
Sift	Benign	0.033	D
Sift4G	Benign	0.15	T
Polyphen		0.010	B
Vest4		0.36
MutPred		0.45		Loss of disorder (P = 0.0056);
MVP		0.13
MPC		0.0097
ClinPred		0.10	T
GERP RS		1.2
Varity_R		0.028
gMVP		0.036

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: chr21-31797773;