13-45967812-T-C

Position:

• chr13-45967812-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001330564.2(ZC3H13):​c.4013A>G​(p.Asp1338Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZC3H13 NM_001330564.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.05

Genes affected

ZC3H13 (HGNC:20368): (zinc finger CCCH-type containing 13) Enables RNA binding activity. Involved in mRNA methylation. Located in nuclear speck. Part of RNA N6-methyladenosine methyltransferase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZC3H13	NM_001330564.2	c.4013A>G	p.Asp1338Gly	missense_variant	15/19	ENST00000679008.1	NP_001317493.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZC3H13	ENST00000679008.1	c.4013A>G	p.Asp1338Gly	missense_variant	15/19		NM_001330564.2	ENSP00000503994	A2
ZC3H13	ENST00000282007.7	c.4013A>G	p.Asp1338Gly	missense_variant	15/17	1		ENSP00000282007	P2
ZC3H13	ENST00000242848.8	c.4013A>G	p.Asp1338Gly	missense_variant	15/19	5		ENSP00000242848	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 21, 2021

The c.4013A>G (p.D1338G) alteration is located in exon 15 (coding exon 14) of the ZC3H13 gene. This alteration results from a A to G substitution at nucleotide position 4013, causing the aspartic acid (D) at amino acid position 1338 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Benign	-0.080	T
BayesDel_noAF	Benign	-0.35
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Benign	0.027	T;.
Eigen	Benign	-0.013
Eigen_PC	Benign	0.039
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.68	T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;N
MutationTaster	Benign	1.0	D;D;D
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.040
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.014	D;D
Polyphen		0.46	P;P
Vest4		0.20
MutPred		0.25		Loss of helix (P = 0.0068);Loss of helix (P = 0.0068);
MVP		0.10
MPC		0.45
ClinPred		0.64	D
GERP RS		4.5
Varity_R		0.19
gMVP		0.017

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.45		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.45		Position offset: 1

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

Publications

LitVar

Other links and lift over

dbSNP: rs1952221433; hg19: chr13-46541947;