18-62523600-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_017742.6(ZCCHC2):​c.176C>T​(p.Pro59Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000207 in 144,992 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P59R) has been classified as Likely benign.

• Frequency: Genomes: 𝑓 0.000021 (0 hom., cov: 31)
• Consequence: ZCCHC2 NM_017742.6 missense
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.14517829).

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>T	p.Pro59Leu	missense	Exon 1 of 14	NP_060212.4
	ZCCHC2	NR_126534.2		n.576C>T		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>T	p.Pro59Leu	missense	Exon 1 of 14	ENSP00000269499.4	Q9C0B9-1
	ZCCHC2	ENST00000963441.1		c.176C>T	p.Pro59Leu	missense	Exon 1 of 14	ENSP00000633500.1
	ZCCHC2	ENST00000585873.5	TSL:1	n.-68C>T		upstream_gene	N/A	ENSP00000468789.1	K7ESN2

Frequencies

GnomAD3 genomes AF: 0.0000207 AC: 3 AN: 144992 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000608

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 34

GnomAD4 genome AF: 0.0000207 AC: 3 AN: 144992 Hom.: 0 Cov.: 31 AF XY: 0.0000426 AC XY: 3 AN XY: 70472

African (AFR) AF: 0.00 AC: 0 AN: 40424

American (AMR) AF: 0.00 AC: 0 AN: 14672

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

East Asian (EAS) AF: 0.000608 AC: 3 AN: 4936

South Asian (SAS) AF: 0.00 AC: 0 AN: 4712

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65364

Other (OTH) AF: 0.00 AC: 0 AN: 2000

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.035	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	14
DANN	Benign	0.97
DEOGEN2	Benign	0.0046	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.33	T
M_CAP	Pathogenic	0.76	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.26
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.76	N
REVEL	Benign	0.27
Sift	Benign	0.10	T
Sift4G	Uncertain	0.0050	D
Polyphen		0.0010	B
Vest4		0.30
MutPred		0.22		Loss of glycosylation at P59 (P = 0.0075)
MVP		0.23
MPC		0.043
ClinPred		0.042	T
GERP RS		0.62
PromoterAI		-0.0064	Neutral
Varity_R		0.049
gMVP		0.23

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;