19-47066434-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_015168.2(ZC3H4):c.3834C>T(p.Arg1278=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000767 in 1,571,922 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0037 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00045 (5 hom.)
• Consequence: ZC3H4 NM_015168.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.83

Genes affected

ZC3H4 (HGNC:17808): (zinc finger CCCH-type containing 4) This gene encodes a member of a family of CCCH (C-x8-C-x5-C-x3-H type) zinc finger domain-containing proteins. These zinc finger domains, which coordinate zinc finger binding and are characterized by three cysteine residues and one histidine residue, are nucleic acid-binding. Other family members are known to function in post-transcriptional regulation. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 19-47066434-G-A is Benign according to our data. Variant chr19-47066434-G-A is described in ClinVar as [Benign]. Clinvar id is 3053829.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.83 with no splicing effect.
• BS2: High AC in GnomAd at 558 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZC3H4	NM_015168.2	c.3834C>T	p.Arg1278=	synonymous_variant	15/15	ENST00000253048.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZC3H4	ENST00000253048.10	c.3834C>T	p.Arg1278=	synonymous_variant	15/15	1	NM_015168.2	P1
ZC3H4	ENST00000601973.1	c.2655C>T	p.Arg885=	synonymous_variant	8/8	5
ZC3H4	ENST00000594019.5	n.1684C>T		non_coding_transcript_exon_variant	7/7	2

Frequencies

GnomAD3 genomes AF: 0.00367 AC: 558 AN: 152108 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.0128

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00107 AC: 204 AN: 191484 Hom.: 1 AF XY: 0.000698 AC XY: 72 AN XY: 103220

Gnomad AFR exome AF: 0.0143

Gnomad AMR exome AF: 0.000850

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000231

Gnomad OTH exome AF: 0.000213

GnomAD4 exome AF: 0.000452 AC: 642 AN: 1419696 Hom.: 5 Cov.: 31 AF XY: 0.000394 AC XY: 277 AN XY: 702462

Gnomad4 AFR exome AF: 0.0157

Gnomad4 AMR exome AF: 0.000647

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000252

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000256

Gnomad4 OTH exome AF: 0.00114

GnomAD4 genome AF: 0.00371 AC: 564 AN: 152226 Hom.: 3 Cov.: 32 AF XY: 0.00359 AC XY: 267 AN XY: 74430

Gnomad4 AFR AF: 0.0129

Gnomad4 AMR AF: 0.00111

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.000108 Hom.: 0

Bravo AF: 0.00406

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

ZC3H4-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 07, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	0.0020
Dann	Benign	0.62

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: rs142249528; hg19: chr19-47569691;