NM_181622.2:c.43C>T

Variant names:

• chr21-30425870-G-A
• NM_181622.2:c.43C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_181622.2(KRTAP13-3):​c.43C>T​(p.His15Tyr) 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. 16/22 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: KRTAP13-3 NM_181622.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.578
• Publications: 0 publications found

Genes affected

KRTAP13-3 (HGNC:18925): (keratin associated protein 13-3) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

LOC105372772 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05172828).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181622.2. 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
	KRTAP13-3	NM_181622.2	MANE Select	c.43C>T	p.His15Tyr	missense	Exon 1 of 1	NP_853653.1	Q3SY46

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP13-3	ENST00000390690.3	TSL:6 MANE Select	c.43C>T	p.His15Tyr	missense	Exon 1 of 1	ENSP00000375109.2	Q3SY46

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	0.060
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.057
DANN	Benign	0.38
DEOGEN2	Benign	0.016	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0092	N
LIST_S2	Benign	0.031	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-0.97	N
PhyloP100		-0.58
PrimateAI	Benign	0.27	T
PROVEAN	Benign	1.8	N
REVEL	Benign	0.0050
Sift	Benign	0.24	T
Sift4G	Benign	0.78	T
Polyphen		0.0010	B
Vest4		0.20
MutPred		0.33		Loss of sheet (P = 0.1398)
MVP		0.030
MPC		0.0090
ClinPred		0.12	T
GERP RS		-3.8
PromoterAI		0.020	Neutral
Varity_R		0.034
gMVP		0.034
Mutation Taster		=100/0	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: chr21-31798188;