21-30430727-G-C

Variant names:

• chr21-30430727-G-C
• rs148941861
• NM_181600.3:c.452G>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_181600.3(KRTAP13-4):​c.452G>C​(p.Cys151Ser) 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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: KRTAP13-4 NM_181600.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0300

Genes affected

KRTAP13-4 (HGNC:18926): (keratin associated protein 13-4) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

LOC105372772 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.776

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP13-4	NM_181600.3	c.452G>C	p.Cys151Ser	missense_variant	Exon 1 of 1	ENST00000334068.4	NP_853631.1
LOC105372772	XR_937653.3	n.196-37367C>G		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRTAP13-4	ENST00000334068.4	c.452G>C	p.Cys151Ser	missense_variant	Exon 1 of 1	6	NM_181600.3	ENSP00000334834.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	14
DANN	Benign	0.80
DEOGEN2	Benign	0.029	T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0057	T
MetaRNN	Pathogenic	0.78	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.1	M
PrimateAI	Benign	0.32	T
PROVEAN	Pathogenic	-7.3	D
REVEL	Benign	0.062
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.19
MutPred		0.89		Gain of glycosylation at C151 (P = 0.0103);
MVP		0.085
MPC		0.12
ClinPred		0.49	T
GERP RS		-0.69
Varity_R		0.27
gMVP		0.16

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

Publications

LitVar

Other links and lift over

dbSNP: rs148941861; hg19: chr21-31803045;