rs563696641

Variant names:

• chr18-62523648-C-A
• rs563696641
• NM_017742.6:c.224C>A

Your query was ambiguous. Multiple possible variants found:

• chr18-62523648-C-A
• chr18-62523648-C-G
• chr18-62523648-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017742.6(ZCCHC2):​c.224C>A​(p.Ala75Glu) 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. 13/21 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: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZCCHC2 NM_017742.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08985755).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZCCHC2	NM_017742.6	c.224C>A	p.Ala75Glu	missense_variant	Exon 1 of 14	ENST00000269499.10	NP_060212.4
ZCCHC2	NR_126534.2	n.624C>A		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.224C>A	p.Ala75Glu	missense_variant	Exon 1 of 14	5	NM_017742.6	ENSP00000269499.4
ZCCHC2	ENST00000588676.1	c.29C>A	p.Ala10Glu	missense_variant	Exon 1 of 1	6		ENSP00000465548.1
ZCCHC2	ENST00000585873.5	n.-20C>A		upstream_gene_variant		1		ENSP00000468789.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1147164 Hom.: 0 Cov.: 66 AF XY: 0.00 AC XY: 0 AN XY: 554160

Gnomad4 AFR exome AF: 0.00

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.0034	T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.33	T
M_CAP	Uncertain	0.091	D
MetaRNN	Benign	0.090	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.22	N
REVEL	Benign	0.010
Sift	Benign	0.081	T
Sift4G	Benign	0.32	T
Polyphen		0.0010	B
Vest4		0.17
MutPred		0.29		Gain of loop (P = 0.0166);
MVP		0.030
MPC		0.047
ClinPred		0.18	T
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Varity_R		0.085
gMVP		0.17

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

LitVar

Other links and lift over

dbSNP: rs563696641; hg19: chr18-60190881;