21-30747030-C-A

Variant names:

• chr21-30747030-C-A
• NM_181617.3:c.173G>T

Variant summary

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

The NM_181617.3(KRTAP21-2):​c.173G>T​(p.Gly58Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,358 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 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: 0.0000021 (0 hom.)
• Consequence: KRTAP21-2 NM_181617.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0560

Genes affected

KRTAP21-2 (HGNC:18946): (keratin associated protein 21-2) 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=0.0926722).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP21-2	NM_181617.3	c.173G>T	p.Gly58Val	missense_variant	Exon 1 of 1	ENST00000333892.3	NP_853648.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRTAP21-2	ENST00000333892.3	c.173G>T	p.Gly58Val	missense_variant	Exon 1 of 1	6	NM_181617.3	ENSP00000334287.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461358 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726992

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000672

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: 0.00

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

Mar 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.173G>T (p.G58V) alteration is located in exon 1 (coding exon 1) of the KRTAP21-2 gene. This alteration results from a G to T substitution at nucleotide position 173, causing the glycine (G) at amino acid position 58 to be replaced by a valine (V). 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	0.22
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	8.7
DANN	Benign	0.54
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.98
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.093	T
MetaSVM	Benign	-1.0	T
PROVEAN	Pathogenic	-7.3	D
REVEL	Benign	0.041
Sift	Benign	0.38	T
Sift4G	Pathogenic	0.0010	D
Polyphen		0.094	B
Vest4		0.23
MutPred		0.39		Gain of sheet (P = 0.0125);
MVP		0.25
MPC		0.31
ClinPred		0.086	T
GERP RS		1.4
Varity_R		0.19
gMVP		0.17

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: chr21-32119348;