rs1914170080

Variant names:

• chr18-62523615-C-T
• rs1914170080
• NM_017742.6:c.191C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017742.6(ZCCHC2):​c.191C>T​(p.Pro64Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000681 in 146,748 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★).

• Frequency:
  • Genomes: 𝑓 0.0000068 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZCCHC2 NM_017742.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.539
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.041426033).

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.191C>T	p.Pro64Leu	missense	Exon 1 of 14	NP_060212.4
	ZCCHC2	NR_126534.2		n.591C>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.191C>T	p.Pro64Leu	missense	Exon 1 of 14	ENSP00000269499.4	Q9C0B9-1
	ZCCHC2	ENST00000963441.1		c.191C>T	p.Pro64Leu	missense	Exon 1 of 14	ENSP00000633500.1
	ZCCHC2	ENST00000585873.5	TSL:1	n.-53C>T		upstream_gene	N/A	ENSP00000468789.1	K7ESN2

Frequencies

GnomAD3 genomes AF: 0.00000681 AC: 1 AN: 146748 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: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1033904 Hom.: 0 Cov.: 66 AF XY: 0.00 AC XY: 0 AN XY: 487682

African (AFR) AF: 0.00 AC: 0 AN: 21160

American (AMR) AF: 0.00 AC: 0 AN: 6794

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12262

East Asian (EAS) AF: 0.00 AC: 0 AN: 22714

South Asian (SAS) AF: 0.00 AC: 0 AN: 18870

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 18634

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2684

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 890612

Other (OTH) AF: 0.00 AC: 0 AN: 40174

GnomAD4 genome AF: 0.00000681 AC: 1 AN: 146748 Hom.: 0 Cov.: 31 AF XY: 0.0000140 AC XY: 1 AN XY: 71354

African (AFR) AF: 0.00 AC: 0 AN: 40754

American (AMR) AF: 0.00 AC: 0 AN: 14816

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3402

East Asian (EAS) AF: 0.00 AC: 0 AN: 5034

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8724

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65970

Other (OTH) AF: 0.00 AC: 0 AN: 2024

Alfa AF: 0.00 Hom.: 0

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	0.14
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0034	T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.068	N
LIST_S2	Benign	0.40	T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.54
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.90	N
REVEL	Benign	0.055
Sift	Benign	0.23	T
Sift4G	Uncertain	0.028	D
Polyphen		0.0	B
Vest4		0.17
MutPred		0.18		Loss of relative solvent accessibility (P = 0.008)
MVP		0.014
MPC		0.043
ClinPred		0.11	T
GERP RS		1.7
PromoterAI		0.00040	Neutral
Varity_R		0.040
gMVP		0.24
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

dbSNP: rs1914170080; hg19: chr18-60190848;