7-156654688-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_030936.4(RNF32):​c.387C>G​(p.Ile129Met) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

RNF32
NM_030936.4 missense

Scores

7
5
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.433
Variant links:
Genes affected
RNF32 (HGNC:17118): (ring finger protein 32) The protein encoded by this gene contains two RING ring finger motifs. RING finger motifs are present in a variety of functionally distinct proteins and are known to be involved in protein-DNA or protein-protein interactions. This gene was found to be expressed during spermatogenesis, most likely in spermatocytes and/or in spermatids. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Apr 2015]
RNF32-AS1 (HGNC:40798): (RNF32 antisense RNA 1)

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.845

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RNF32NM_030936.4 linkuse as main transcriptc.387C>G p.Ile129Met missense_variant 4/9 ENST00000317955.10 NP_112198.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RNF32ENST00000317955.10 linkuse as main transcriptc.387C>G p.Ile129Met missense_variant 4/91 NM_030936.4 ENSP00000315950 P1Q9H0A6-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

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 GeneticsAug 04, 2021The c.387C>G (p.I129M) alteration is located in exon 4 (coding exon 3) of the RNF32 gene. This alteration results from a C to G substitution at nucleotide position 387, causing the isoleucine (I) at amino acid position 129 to be replaced by a methionine (M). 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
Pathogenic
0.80
BayesDel_addAF
Pathogenic
0.35
D
BayesDel_noAF
Pathogenic
0.26
CADD
Benign
17
DANN
Uncertain
0.99
DEOGEN2
Benign
0.25
.;T;T;T;.;T;.
Eigen
Benign
0.057
Eigen_PC
Benign
-0.15
FATHMM_MKL
Benign
0.49
N
LIST_S2
Benign
0.85
T;.;.;.;T;T;D
M_CAP
Benign
0.077
D
MetaRNN
Pathogenic
0.84
D;D;D;D;D;D;D
MetaSVM
Uncertain
0.61
D
MutationAssessor
Pathogenic
3.5
.;M;M;M;.;M;M
MutationTaster
Benign
1.0
D;D;D;D;D;D;D
PrimateAI
Uncertain
0.56
T
PROVEAN
Uncertain
-2.8
D;D;D;D;D;D;D
REVEL
Pathogenic
0.70
Sift
Pathogenic
0.0
D;D;D;D;D;D;D
Sift4G
Uncertain
0.0020
D;D;D;D;D;D;D
Polyphen
1.0, 0.99
.;D;D;D;D;D;D
Vest4
0.80, 0.81, 0.81
MutPred
0.81
Gain of disorder (P = 0.0341);Gain of disorder (P = 0.0341);Gain of disorder (P = 0.0341);Gain of disorder (P = 0.0341);Gain of disorder (P = 0.0341);Gain of disorder (P = 0.0341);Gain of disorder (P = 0.0341);
MVP
0.77
MPC
0.62
ClinPred
0.99
D
GERP RS
-2.3
Varity_R
0.78
gMVP
0.68

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.080
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: rs1799329074; hg19: chr7-156447382; API