21-30616521-G-A

Position:

• chr21-30616521-G-A

Variant summary

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

The NM_181615.2(KRTAP20-1):​c.67G>A​(p.Gly23Ser) 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. 12/19 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: KRTAP20-1 NM_181615.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.34

Genes affected

KRTAP20-1 (HGNC:18943): (keratin associated protein 20-1) 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=0.25024056).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP20-1	NM_181615.2	c.67G>A	p.Gly23Ser	missense_variant	1/1	ENST00000334664.3	NP_853646.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTAP20-1	ENST00000334664.3	c.67G>A	p.Gly23Ser	missense_variant	1/1	6	NM_181615.2	ENSP00000335503.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

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 26, 2022

The c.67G>A (p.G23S) alteration is located in exon 1 (coding exon 1) of the KRTAP20-1 gene. This alteration results from a G to A substitution at nucleotide position 67, causing the glycine (G) at amino acid position 23 to be replaced by a serine (S). 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	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	13
DANN	Benign	0.92
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.23	N
M_CAP	Benign	0.00098	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.1	T
PROVEAN	Pathogenic	-6.0	D
REVEL	Benign	0.029
Sift4G	Uncertain	0.028	D
Polyphen		1.0	D
Vest4		0.34
MutPred		0.27		Gain of glycosylation at G23 (P = 0.0448);
MVP		0.35
MPC		0.0033
ClinPred		0.46	T
GERP RS		1.7
Varity_R		0.74
gMVP		0.051

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr21-31988840;