21-30425792-A-G

Variant names:

• chr21-30425792-A-G
• NM_181622.2:c.121T>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_181622.2(KRTAP13-3):​c.121T>C​(p.Cys41Arg) 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 pathogenic outcome for this variant. 14/22 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: 1.03
• 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: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.906

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.121T>C	p.Cys41Arg	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.121T>C	p.Cys41Arg	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	0.17
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	19
DANN	Benign	0.75
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0045	T
MetaRNN	Pathogenic	0.91	D
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.9	L
PhyloP100		1.0
PrimateAI	Benign	0.39	T
PROVEAN	Pathogenic	-6.5	D
REVEL	Benign	0.26
Sift	Benign	0.15	T
Sift4G	Benign	0.12	T
Polyphen		0.17	B
Vest4		0.59
MutPred		0.84		Gain of phosphorylation at S44 (P = 0.0559)
MVP		0.085
MPC		0.013
ClinPred		0.26	T
GERP RS		3.6
PromoterAI		-0.0084	Neutral
Varity_R		0.46
gMVP		0.15
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr21-31798110;