rs1015613321

Variant names:

• chr18-62523516-C-G
• NM_017742.6:c.92C>G

Your query was ambiguous. Multiple possible variants found:

• chr18-62523516-C-G
• chr18-62523516-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017742.6(ZCCHC2):​c.92C>G​(p.Ala31Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000604 in 827,218 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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: 28)
  • Exomes 𝑓: 0.0000060 (0 hom.)
• Consequence: ZCCHC2 NM_017742.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.415

Genes affected

ZCCHC2 (HGNC:22916): (zinc finger CCHC-type containing 2) Predicted to enable nucleic acid binding activity; phosphatidylinositol binding activity; and zinc ion binding activity. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.054226846).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZCCHC2	NM_017742.6	c.92C>G	p.Ala31Gly	missense_variant	Exon 1 of 14	ENST00000269499.10	NP_060212.4
ZCCHC2	NR_126534.2	n.492C>G		non_coding_transcript_exon_variant	Exon 1 of 15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZCCHC2	ENST00000269499.10	c.92C>G	p.Ala31Gly	missense_variant	Exon 1 of 14	5	NM_017742.6	ENSP00000269499.4
ZCCHC2	ENST00000585873.5	n.-152C>G		upstream_gene_variant		1		ENSP00000468789.1
ZCCHC2	ENST00000588676.1	c.-104C>G		upstream_gene_variant		6		ENSP00000465548.1

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome AF: 0.00000604 AC: 5 AN: 827218 Hom.: 0 Cov.: 36 AF XY: 0.0000131 AC XY: 5 AN XY: 382962

Gnomad4 AFR exome AF: 0.0000641

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000397

Gnomad4 OTH exome AF: 0.0000368

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.0065	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.32	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.22	N
REVEL	Benign	0.13
Sift	Benign	0.030	D
Sift4G	Benign	0.45	T
Polyphen		0.0	B
Vest4		0.065
MutPred		0.17		Loss of stability (P = 0.1348);
MVP		0.076
MPC		0.042
ClinPred		0.093	T
GERP RS		0.58
Varity_R		0.051
gMVP		0.12

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-60190749;