19-47066875-C-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_015168.2(ZC3H4):c.3393G>C(p.Leu1131=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00253 in 1,598,566 control chromosomes in the GnomAD database, including 104 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.014 (51 hom., cov: 33)
  • Exomes 𝑓: 0.0014 (53 hom.)
• Consequence: ZC3H4 NM_015168.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0200

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 19-47066875-C-G is Benign according to our data. Variant chr19-47066875-C-G is described in ClinVar as [Benign]. Clinvar id is 769023.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.02 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0136 (2065/152322) while in subpopulation AFR AF= 0.0469 (1952/41578). AF 95% confidence interval is 0.0452. There are 51 homozygotes in gnomad4. There are 962 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 2063 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZC3H4	NM_015168.2	c.3393G>C	p.Leu1131=	synonymous_variant	15/15	ENST00000253048.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZC3H4	ENST00000253048.10	c.3393G>C	p.Leu1131=	synonymous_variant	15/15	1	NM_015168.2	P1
ZC3H4	ENST00000601973.1	c.2214G>C	p.Leu738=	synonymous_variant	8/8	5
ZC3H4	ENST00000594019.5	n.1243G>C		non_coding_transcript_exon_variant	7/7	2

Frequencies

GnomAD3 genomes AF: 0.0136 AC: 2063 AN: 152204 Hom.: 52 Cov.: 33

Gnomad AFR AF: 0.0470

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00543

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: 0.000162

Gnomad OTH AF: 0.00907

GnomAD3 exomes AF: 0.00335 AC: 758 AN: 226384 Hom.: 16 AF XY: 0.00269 AC XY: 337 AN XY: 125318

Gnomad AFR exome AF: 0.0500

Gnomad AMR exome AF: 0.00216

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000332

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000673

Gnomad OTH exome AF: 0.00141

GnomAD4 exome AF: 0.00137 AC: 1975 AN: 1446244 Hom.: 53 Cov.: 33 AF XY: 0.00123 AC XY: 886 AN XY: 719788

Gnomad4 AFR exome AF: 0.0474

Gnomad4 AMR exome AF: 0.00245

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000349

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000603

Gnomad4 OTH exome AF: 0.00326

GnomAD4 genome AF: 0.0136 AC: 2065 AN: 152322 Hom.: 51 Cov.: 33 AF XY: 0.0129 AC XY: 962 AN XY: 74478

Gnomad4 AFR AF: 0.0469

Gnomad4 AMR AF: 0.00542

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.00898

Alfa AF: 0.00571 Hom.: 5

Bravo AF: 0.0154

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 19, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
Cadd	Benign	1.7
Dann	Benign	0.62
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs184799751; hg19: chr19-47570132;