4-25356487-G-C

Variant names:

• chr4-25356487-G-C
• rs13149511
• NM_024936.3:c.1011+4798G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024936.3(ZCCHC4):​c.1011+4798G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 30)
• Consequence: ZCCHC4 NM_024936.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.75
• Publications: 5 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZCCHC4	NM_024936.3	c.1011+4798G>C		intron_variant	Intron 8 of 12	ENST00000302874.9	NP_079212.2
ZCCHC4	XM_011513835.3	c.1056+3312G>C		intron_variant	Intron 9 of 13		XP_011512137.1
ZCCHC4	XM_017008129.3	c.760-5372G>C		intron_variant	Intron 6 of 10		XP_016863618.1
ZCCHC4	XR_925324.4	n.1092+3312G>C		intron_variant	Intron 9 of 13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZCCHC4	ENST00000302874.9	c.1011+4798G>C		intron_variant	Intron 8 of 12	1	NM_024936.3	ENSP00000303468.4
ZCCHC4	ENST00000507760.5	n.687-5372G>C		intron_variant	Intron 5 of 8	1		ENSP00000422115.1
ZCCHC4	ENST00000505412.1	c.603+4798G>C		intron_variant	Intron 5 of 9	3		ENSP00000422269.1

Frequencies

GnomAD3 genomes Cov.: 30

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

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	20
DANN	Benign	0.77
PhyloP100		2.8

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: rs13149511; hg19: chr4-25358109;