rs376452593

Variant names:

• chr8-143441023-C-A
• rs376452593
• NM_015117.3:c.2405G>T

Your query was ambiguous. Multiple possible variants found:

• chr8-143441023-C-A
• chr8-143441023-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015117.3(ZC3H3):​c.2405G>T​(p.Arg802Leu) 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. 14/22 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. R802H) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 35)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZC3H3 NM_015117.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.650
• Publications: 0 publications found

Genes affected

ZC3H3 (HGNC:28972): (zinc finger CCCH-type containing 3) Predicted to enable SMAD binding activity. Involved in regulation of mRNA polyadenylation. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07334685).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZC3H3	NM_015117.3	c.2405G>T	p.Arg802Leu	missense_variant	Exon 10 of 12	ENST00000262577.6	NP_055932.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZC3H3	ENST00000262577.6	c.2405G>T	p.Arg802Leu	missense_variant	Exon 10 of 12	1	NM_015117.3	ENSP00000262577.5

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1327464 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 653544

African (AFR) AF: 0.00 AC: 0 AN: 26278

American (AMR) AF: 0.00 AC: 0 AN: 21430

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20642

East Asian (EAS) AF: 0.00 AC: 0 AN: 31656

South Asian (SAS) AF: 0.00 AC: 0 AN: 67568

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44924

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5336

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1055018

Other (OTH) AF: 0.00 AC: 0 AN: 54612

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.029	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.055	D
MetaRNN	Benign	0.073	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.65
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.077
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.056	T
Polyphen		0.038	B
Vest4		0.38
MutPred		0.24		Loss of MoRF binding (P = 0.0526);
MVP		0.043
ClinPred		0.92	D
GERP RS		2.9
Varity_R		0.19
gMVP		0.39
Mutation Taster		=83/17	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: rs376452593; hg19: chr8-144523193;