rs763258711

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6

The NM_014153.4(ZC3H7A):​c.2258G>T​(p.Arg753Leu) 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. Variant has been reported in Lovd as Likely benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R753H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

ZC3H7A
NM_014153.4 missense

Scores

2
4
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.35
Variant links:
Genes affected
ZC3H7A (HGNC:30959): (zinc finger CCCH-type containing 7A) Enables miRNA binding activity. Involved in production of miRNAs involved in gene silencing by miRNA. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.16806924).
BP6
Variant 16-11761467-C-A is Benign according to our data. Variant chr16-11761467-C-A is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZC3H7ANM_014153.4 linkc.2258G>T p.Arg753Leu missense_variant Exon 19 of 23 ENST00000355758.9 NP_054872.2 Q8IWR0-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZC3H7AENST00000355758.9 linkc.2258G>T p.Arg753Leu missense_variant Exon 19 of 23 1 NM_014153.4 ENSP00000347999.4 Q8IWR0-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251390
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135854
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.63
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.49
CADD
Uncertain
24
DANN
Uncertain
0.98
DEOGEN2
Benign
0.20
T;T;.
Eigen
Benign
-0.23
Eigen_PC
Benign
-0.073
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.89
.;D;D
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.17
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.5
L;L;.
PrimateAI
Uncertain
0.53
T
PROVEAN
Uncertain
-3.8
D;D;.
REVEL
Benign
0.049
Sift
Benign
0.045
D;D;.
Sift4G
Benign
0.092
T;T;.
Polyphen
0.0030
B;B;.
Vest4
0.36
MutPred
0.38
Loss of disorder (P = 0.0196);Loss of disorder (P = 0.0196);.;
MVP
0.14
MPC
0.67
ClinPred
0.85
D
GERP RS
2.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.14
gMVP
0.53

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

Publications

LitVar

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

Other links and lift over

dbSNP: rs763258711; hg19: chr16-11855323; API