21-30616614-G-T

Variant names:

• chr21-30616614-G-T
• rs377683936
• NM_181615.2:c.160G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_181615.2(KRTAP20-1):​c.160G>T​(p.Gly54Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G54R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KRTAP20-1 NM_181615.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16
• Publications: 0 publications found

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]

ENSG00000308278 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181615.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP20-1	NM_181615.2	MANE Select	c.160G>T	p.Gly54Cys	missense	Exon 1 of 1	NP_853646.1	Q3LI63

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP20-1	ENST00000334664.3	TSL:6 MANE Select	c.160G>T	p.Gly54Cys	missense	Exon 1 of 1	ENSP00000335503.2	Q3LI63
	ENSG00000308278	ENST00000832954.1		n.176-3215G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.085	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	16
DANN	Benign	0.82
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.046	N
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.54	D
MetaSVM	Benign	-0.93	T
PhyloP100		1.2
PROVEAN	Pathogenic	-9.0	D
REVEL	Benign	0.11
Sift4G	Uncertain	0.010	D
Polyphen		1.0	D
Vest4		0.53
MutPred		0.40		Loss of disorder (P = 8e-04)
MVP		0.51
MPC		0.0031
ClinPred		0.86	D
GERP RS		0.16
PromoterAI		0.0086	Neutral
Varity_R		0.78
gMVP		0.030
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs377683936; hg19: chr21-31988933;