NM_181620.2:c.55G>A

Variant names:

• chr21-30601175-G-A
• NM_181620.2:c.55G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_181620.2(KRTAP22-1):​c.55G>A​(p.Gly19Ser) 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. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: KRTAP22-1 NM_181620.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.54
• Publications: 0 publications found

Genes affected

KRTAP22-1 (HGNC:18947): (keratin associated protein 22-1) 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3260706).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181620.2. 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
	KRTAP22-1	NM_181620.2	MANE Select	c.55G>A	p.Gly19Ser	missense	Exon 1 of 1	NP_853651.1	Q3MIV0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP22-1	ENST00000334680.3	TSL:6 MANE Select	c.55G>A	p.Gly19Ser	missense	Exon 1 of 1	ENSP00000333887.2	Q3MIV0
	ENSG00000308278	ENST00000832954.1		n.176-18654G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.028	T
Eigen	Benign	0.038
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.5
PROVEAN	Pathogenic	-6.0	D
REVEL	Benign	0.083
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.32
MutPred		0.41		Gain of sheet (P = 0.039)
MVP		0.20
MPC		0.35
ClinPred		0.75	D
GERP RS		4.2
PromoterAI		0.011	Neutral
Varity_R		0.74
gMVP		0.38
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

hg19: chr21-31973494;