12-71611075-G-C

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBS2_Supporting

The NM_144982.5(ZFC3H1):ā€‹c.5752C>Gā€‹(p.Leu1918Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,465,912 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.00010 ( 0 hom., cov: 30)
Exomes š‘“: 0.0000037 ( 0 hom. )

Consequence

ZFC3H1
NM_144982.5 missense

Scores

2
5
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.73
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.09667137).
BS2
High AC in GnomAd4 at 12 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ZFC3H1NM_144982.5 linkuse as main transcriptc.5752C>G p.Leu1918Val missense_variant 33/35 ENST00000378743.9
ZFC3H1XM_047428485.1 linkuse as main transcriptc.4573C>G p.Leu1525Val missense_variant 33/35

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ZFC3H1ENST00000378743.9 linkuse as main transcriptc.5752C>G p.Leu1918Val missense_variant 33/351 NM_144982.5 P1O60293-1
ZFC3H1ENST00000552994.5 linkuse as main transcriptc.*707C>G 3_prime_UTR_variant, NMD_transcript_variant 32/341 O60293-2
ZFC3H1ENST00000547398.1 linkuse as main transcriptn.212C>G non_coding_transcript_exon_variant 1/32
ZFC3H1ENST00000550963.1 linkuse as main transcriptn.180C>G non_coding_transcript_exon_variant 1/25

Frequencies

GnomAD3 genomes
AF:
0.000104
AC:
12
AN:
115814
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00100
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00130
GnomAD4 exome
AF:
0.00000370
AC:
5
AN:
1350040
Hom.:
0
Cov.:
31
AF XY:
0.00000149
AC XY:
1
AN XY:
670220
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000543
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:
0.0000544
GnomAD4 genome
AF:
0.000104
AC:
12
AN:
115872
Hom.:
0
Cov.:
30
AF XY:
0.0000915
AC XY:
5
AN XY:
54648
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00100
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00128
ExAC
AF:
0.00000828
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJun 03, 2022The c.5752C>G (p.L1918V) alteration is located in exon 33 (coding exon 33) of the ZFC3H1 gene. This alteration results from a C to G substitution at nucleotide position 5752, causing the leucine (L) at amino acid position 1918 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.17
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.35
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.048
T
Eigen
Uncertain
0.42
Eigen_PC
Uncertain
0.44
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.80
T
M_CAP
Benign
0.0081
T
MetaRNN
Benign
0.097
T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
0.81
L
MutationTaster
Benign
0.97
D
PrimateAI
Pathogenic
0.79
T
PROVEAN
Benign
-1.1
N
REVEL
Benign
0.10
Sift
Uncertain
0.0070
D
Sift4G
Pathogenic
0.0
D
Polyphen
0.99
D
Vest4
0.41
MutPred
0.21
Gain of catalytic residue at I1916 (P = 0.0103);
MVP
0.082
MPC
1.1
ClinPred
0.77
D
GERP RS
4.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.11
gMVP
0.26

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs201622619; hg19: chr12-72004855; COSMIC: COSV66432804; COSMIC: COSV66432804; API