rs452586

Positions:

• chr6-149458049-G-A
• chr6-149458049-G-C
• chr6-149458049-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_207360.3(ZC3H12D):​c.446-1149C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 146,156 control chromosomes in the GnomAD database, including 10,348 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 0.37 (10348 hom., cov: 27)
• Consequence: ZC3H12D NM_207360.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.278

Genes affected

ZC3H12D (HGNC:21175): (zinc finger CCCH-type containing 12D) Predicted to enable endoribonuclease activity and mRNA binding activity. Involved in negative regulation of G1/S transition of mitotic cell cycle and negative regulation of cell growth. Located in P-body and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZC3H12D	NM_207360.3	c.446-1149C>T		intron_variant		ENST00000409806.8	NP_997243.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZC3H12D	ENST00000409806.8	c.446-1149C>T		intron_variant		1	NM_207360.3	ENSP00000386616	P1

Frequencies

GnomAD3 genomes AF: 0.371 AC: 54122 AN: 146042 Hom.: 10340 Cov.: 27

Gnomad AFR AF: 0.466

Gnomad AMI AF: 0.426

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.265

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.356

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

GnomAD4 genome AF: 0.371 AC: 54168 AN: 146156 Hom.: 10348 Cov.: 27 AF XY: 0.367 AC XY: 26040 AN XY: 70972

Gnomad4 AFR AF: 0.466

Gnomad4 AMR AF: 0.280

Gnomad4 ASJ AF: 0.321

Gnomad4 EAS AF: 0.142

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.370

Gnomad4 NFE AF: 0.363

Gnomad4 OTH AF: 0.356

Alfa AF: 0.241 Hom.: 764

Bravo AF: 0.364

Asia WGS AF: 0.212 AC: 740 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.0
DANN	Benign	0.70

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: rs452586; hg19: chr6-149779185;