4-25345572-T-C

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_024936.3(ZCCHC4):c.711T>C(p.Asp237=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000412 in 1,566,994 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00039 (2 hom.)
• Consequence: ZCCHC4 NM_024936.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.301

Genes affected

ZCCHC4 (HGNC:22917): (zinc finger CCHC-type containing 4) Enables S-adenosyl-L-methionine binding activity; rRNA (adenine-N6-)-methyltransferase activity; and zinc ion binding activity. Involved in positive regulation of translation and rRNA methylation. Located in cytoplasm and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 4-25345572-T-C is Benign according to our data. Variant chr4-25345572-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2654699.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.301 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZCCHC4	NM_024936.3	c.711T>C	p.Asp237=	synonymous_variant	6/13	ENST00000302874.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZCCHC4	ENST00000302874.9	c.711T>C	p.Asp237=	synonymous_variant	6/13	1	NM_024936.3	P1
ZCCHC4	ENST00000505451.5	n.736T>C		non_coding_transcript_exon_variant	6/9	1
ZCCHC4	ENST00000507760.5	c.686+11584T>C		intron_variant, NMD_transcript_variant		1
ZCCHC4	ENST00000505412.1	c.306T>C	p.Asp102=	synonymous_variant	3/10	3

Frequencies

GnomAD3 genomes AF: 0.000663 AC: 101 AN: 152244 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00668

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000844 AC: 194 AN: 229822 Hom.: 0 AF XY: 0.000779 AC XY: 97 AN XY: 124440

Gnomad AFR exome AF: 0.000146

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000626

Gnomad SAS exome AF: 0.000104

Gnomad FIN exome AF: 0.00750

Gnomad NFE exome AF: 0.000218

Gnomad OTH exome AF: 0.000177

GnomAD4 exome AF: 0.000385 AC: 545 AN: 1414632 Hom.: 2 Cov.: 26 AF XY: 0.000394 AC XY: 278 AN XY: 704752

Gnomad4 AFR exome AF: 0.0000308

Gnomad4 AMR exome AF: 0.0000229

Gnomad4 ASJ exome AF: 0.0000394

Gnomad4 EAS exome AF: 0.00111

Gnomad4 SAS exome AF: 0.0000357

Gnomad4 FIN exome AF: 0.00654

Gnomad4 NFE exome AF: 0.000127

Gnomad4 OTH exome AF: 0.000308

GnomAD4 genome AF: 0.000663 AC: 101 AN: 152362 Hom.: 0 Cov.: 32 AF XY: 0.000899 AC XY: 67 AN XY: 74508

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00309

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00668

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000283 Hom.: 0

Bravo AF: 0.000219

Asia WGS AF: 0.00664 AC: 23 AN: 3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2022

ZCCHC4: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
Cadd	Benign	6.8
Dann	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs374438086; hg19: chr4-25347194;