12-71614877-C-G

Variant names:

• chr12-71614877-C-G
• NM_144982.5:c.5317G>C

Variant summary

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

The NM_144982.5(ZFC3H1):​c.5317G>C​(p.Gly1773Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZFC3H1 NM_144982.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.57
• Publications: 0 publications found

Genes affected

ZFC3H1 (HGNC:28328): (zinc finger C3H1-type containing) Predicted to enable metal ion binding activity. Predicted to be involved in RNA processing. Located in nucleus. Part of exosome (RNase complex). [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144982.5. 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
	ZFC3H1	NM_144982.5	MANE Select	c.5317G>C	p.Gly1773Arg	missense	Exon 29 of 35	NP_659419.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFC3H1	ENST00000378743.9	TSL:1 MANE Select	c.5317G>C	p.Gly1773Arg	missense	Exon 29 of 35	ENSP00000368017.4	O60293-1
	ZFC3H1	ENST00000552994.5	TSL:1	n.5317G>C		non_coding_transcript_exon	Exon 29 of 34	ENSP00000446995.1	O60293-2
	ZFC3H1	ENST00000546475.1	TSL:3	n.272G>C		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	Pathogenic	0.96
BayesDel_addAF	Uncertain	0.067	T
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.049	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.61	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		4.6
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.19
Sift	Uncertain	0.028	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.62
MutPred		0.57		Gain of catalytic residue at M1776 (P = 0)
MVP		0.043
MPC		1.2
ClinPred		0.92	D
GERP RS		5.2
Varity_R		0.38
gMVP		0.54
Mutation Taster		=62/38	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

hg19: chr12-72008657;