21-30372156-G-T

Variant names:

• chr21-30372156-G-T
• rs201103813
• NM_181621.4:c.58C>A

Variant summary

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

The NM_181621.4(KRTAP13-2):​c.58C>A​(p.Arg20Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: KRTAP13-2 NM_181621.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40

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 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=0.05918601).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP13-2	NM_181621.4	c.58C>A	p.Arg20Ser	missense_variant	Exon 1 of 1	ENST00000399889.4	NP_853652.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRTAP13-2	ENST00000399889.4	c.58C>A	p.Arg20Ser	missense_variant	Exon 1 of 1	6	NM_181621.4	ENSP00000382777.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000119 AC: 3 AN: 251084 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135658

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461852 Hom.: 0 Cov.: 33 AF XY: 0.00000550 AC XY: 4 AN XY: 727224

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.033
DANN	Benign	0.50
DEOGEN2	Benign	0.0086	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.088	T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.6	M
PrimateAI	Benign	0.18	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.020
Sift	Benign	0.41	T
Sift4G	Benign	0.41	T
Polyphen		0.0070	B
Vest4		0.086
MutPred		0.34		Gain of phosphorylation at R20 (P = 0.0287);
MVP		0.085
MPC		0.040
ClinPred		0.025	T
GERP RS		0.21
Varity_R		0.12
gMVP		0.040

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

LitVar

Other links and lift over

dbSNP: rs201103813; hg19: chr21-31744474;