chr8-78666161-G-T

Variant names:

• chr8-78666161-G-T
• rs1010212735
• NM_016010.3:c.13G>T

Variant summary

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

The NM_016010.3(ZC2HC1A):​c.13G>T​(p.Glu5*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZC2HC1A NM_016010.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.99
• Publications: 0 publications found

Genes affected

ZC2HC1A (HGNC:24277): (zinc finger C2HC-type containing 1A) Predicted to enable metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000286675 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZC2HC1A	NM_016010.3	c.13G>T	p.Glu5*	stop_gained	Exon 1 of 9	ENST00000263849.9	NP_057094.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZC2HC1A	ENST00000263849.9	c.13G>T	p.Glu5*	stop_gained	Exon 1 of 9	1	NM_016010.3	ENSP00000263849.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1422352 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 703308

African (AFR) AF: 0.00 AC: 0 AN: 32984

American (AMR) AF: 0.00 AC: 0 AN: 38030

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25342

East Asian (EAS) AF: 0.00 AC: 0 AN: 38118

South Asian (SAS) AF: 0.00 AC: 0 AN: 80756

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50326

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5444

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1092302

Other (OTH) AF: 0.00 AC: 0 AN: 59050

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.51	D
BayesDel_noAF	Pathogenic	0.50
CADD	Pathogenic	48
DANN	Uncertain	1.0
Eigen	Pathogenic	1.1
Eigen_PC	Pathogenic	0.91
FATHMM_MKL	Uncertain	0.81	D
PhyloP100		4.0
Vest4		0.029
GERP RS		4.9
PromoterAI		0.066	Neutral
Mutation Taster		=20/180	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1010212735; hg19: chr8-79578396;