NM_001330564.2:c.340-1448G>A

Variant names:

• chr13-46022005-C-T
• rs2031633
• NM_001330564.2:c.340-1448G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001330564.2(ZC3H13):​c.340-1448G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 151,614 control chromosomes in the GnomAD database, including 5,132 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.25 (5132 hom., cov: 31)
• Consequence: ZC3H13 NM_001330564.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.328
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZC3H13	NM_001330564.2	c.340-1448G>A		intron_variant	Intron 4 of 18	ENST00000679008.1	NP_001317493.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZC3H13	ENST00000679008.1	c.340-1448G>A		intron_variant	Intron 4 of 18		NM_001330564.2	ENSP00000503994.1
ZC3H13	ENST00000282007.7	c.340-1448G>A		intron_variant	Intron 4 of 16	1		ENSP00000282007.3
ZC3H13	ENST00000242848.8	c.340-1448G>A		intron_variant	Intron 4 of 18	5		ENSP00000242848.4

Frequencies

GnomAD3 genomes AF: 0.250 AC: 37830 AN: 151496 Hom.: 5118 Cov.: 31

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.211

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.250 AC: 37865 AN: 151614 Hom.: 5132 Cov.: 31 AF XY: 0.253 AC XY: 18775 AN XY: 74082

African (AFR) AF: 0.160 AC: 6616 AN: 41398

American (AMR) AF: 0.247 AC: 3769 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 760 AN: 3470

East Asian (EAS) AF: 0.223 AC: 1150 AN: 5164

South Asian (SAS) AF: 0.324 AC: 1563 AN: 4818

European-Finnish (FIN) AF: 0.317 AC: 3341 AN: 10542

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.295 AC: 19951 AN: 67686

Other (OTH) AF: 0.214 AC: 450 AN: 2106

Alfa AF: 0.270 Hom.: 752

Bravo AF: 0.240

Asia WGS AF: 0.251 AC: 872 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.6
DANN	Benign	0.44
PhyloP100		0.33
Mutation Taster		=100/0	polymorphism (auto)

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

dbSNP: rs2031633; hg19: chr13-46596140;