NM_017742.6:c.78C>G

Variant names:

• chr18-62523502-C-G
• NM_017742.6:c.78C>G

Variant summary

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

The NM_017742.6(ZCCHC2):​c.78C>G​(p.Asp26Glu) variant causes a missense 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. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D26N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 0.0000012 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZCCHC2 NM_017742.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.163
• Publications: 0 publications found

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

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 (MetaRNN=0.07663837).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017742.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZCCHC2	NM_017742.6	MANE Select	c.78C>G	p.Asp26Glu	missense	Exon 1 of 14	NP_060212.4
	ZCCHC2	NR_126534.2		n.478C>G		non_coding_transcript_exon	Exon 1 of 15

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZCCHC2	ENST00000269499.10	TSL:5 MANE Select	c.78C>G	p.Asp26Glu	missense	Exon 1 of 14	ENSP00000269499.4	Q9C0B9-1
	ZCCHC2	ENST00000963441.1		c.78C>G	p.Asp26Glu	missense	Exon 1 of 14	ENSP00000633500.1
	ZCCHC2	ENST00000585873.5	TSL:1	n.-166C>G		upstream_gene	N/A	ENSP00000468789.1	K7ESN2

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000118 AC: 1 AN: 847624 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 395582

African (AFR) AF: 0.00 AC: 0 AN: 15848

American (AMR) AF: 0.00 AC: 0 AN: 1538

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6050

East Asian (EAS) AF: 0.00 AC: 0 AN: 3932

South Asian (SAS) AF: 0.00 AC: 0 AN: 21024

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1052

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1708

European-Non Finnish (NFE) AF: 0.00000130 AC: 1 AN: 768628

Other (OTH) AF: 0.00 AC: 0 AN: 27844

GnomAD4 genome Cov.: 28

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0055	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.25	T
M_CAP	Uncertain	0.21	D
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.16
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.10	N
REVEL	Benign	0.075
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.57	T
Polyphen		0.0	B
Vest4		0.064
MutPred		0.14		Gain of helix (P = 0.0325)
MVP		0.076
MPC		0.040
ClinPred		0.36	T
GERP RS		0.96
PromoterAI		0.024	Neutral
Varity_R		0.15
gMVP		0.054
Mutation Taster		=96/4	polymorphism

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

hg19: chr18-60190735;