18-62523600-C-G

Variant names:

• chr18-62523600-C-G
• rs915021992
• NM_017742.6:c.176C>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_017742.6(ZCCHC2):​c.176C>G​(p.Pro59Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00102 in 975,562 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0044 (9 hom., cov: 31)
  • Exomes 𝑓: 0.00043 (0 hom.)
• Consequence: ZCCHC2 NM_017742.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.257
• Publications: 1 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.027944088).
• BP6: Variant 18-62523600-C-G is Benign according to our data. Variant chr18-62523600-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2349280.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

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.176C>G	p.Pro59Arg	missense	Exon 1 of 14	NP_060212.4
	ZCCHC2	NR_126534.2		n.576C>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.176C>G	p.Pro59Arg	missense	Exon 1 of 14	ENSP00000269499.4	Q9C0B9-1
	ZCCHC2	ENST00000963441.1		c.176C>G	p.Pro59Arg	missense	Exon 1 of 14	ENSP00000633500.1
	ZCCHC2	ENST00000585873.5	TSL:1	n.-68C>G		upstream_gene	N/A	ENSP00000468789.1	K7ESN2

Frequencies

GnomAD3 genomes AF: 0.00441 AC: 640 AN: 144990 Hom.: 9 Cov.: 31

Gnomad AFR AF: 0.0147

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0129

Gnomad NFE AF: 0.000214

Gnomad OTH AF: 0.00250

GnomAD4 exome AF: 0.000431 AC: 358 AN: 830524 Hom.: 0 Cov.: 34 AF XY: 0.000421 AC XY: 163 AN XY: 387602

African (AFR) AF: 0.0155 AC: 257 AN: 16614

American (AMR) AF: 0.000293 AC: 1 AN: 3408

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7614

East Asian (EAS) AF: 0.00 AC: 0 AN: 11192

South Asian (SAS) AF: 0.00 AC: 0 AN: 15632

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8358

Middle Eastern (MID) AF: 0.00102 AC: 2 AN: 1952

European-Non Finnish (NFE) AF: 0.0000856 AC: 63 AN: 735858

Other (OTH) AF: 0.00117 AC: 35 AN: 29896

GnomAD4 genome AF: 0.00441 AC: 639 AN: 145038 Hom.: 9 Cov.: 31 AF XY: 0.00425 AC XY: 300 AN XY: 70532

African (AFR) AF: 0.0146 AC: 593 AN: 40500

American (AMR) AF: 0.00163 AC: 24 AN: 14686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3376

East Asian (EAS) AF: 0.00 AC: 0 AN: 4916

South Asian (SAS) AF: 0.00 AC: 0 AN: 4706

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8300

Middle Eastern (MID) AF: 0.0105 AC: 3 AN: 286

European-Non Finnish (NFE) AF: 0.000214 AC: 14 AN: 65354

Other (OTH) AF: 0.00248 AC: 5 AN: 2016

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

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	-0.048	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	14
DANN	Benign	0.92
DEOGEN2	Benign	0.0029	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.23	T
M_CAP	Pathogenic	0.83	D
MetaRNN	Benign	0.028	T
MetaSVM	Benign	-0.61	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.26
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.60	N
REVEL	Benign	0.25
Sift	Benign	0.075	T
Sift4G	Benign	0.13	T
Polyphen		0.53	P
Vest4		0.27
MutPred		0.23		Loss of glycosylation at P59 (P = 0.0075)
MVP		0.45
MPC		0.044
ClinPred		0.13	T
GERP RS		0.62
PromoterAI		0.042	Neutral
Varity_R		0.067
gMVP		0.24
Mutation Taster		=98/2	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

dbSNP: rs915021992; hg19: chr18-60190833;