chr7-156644578-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_030936.4(RNF32):​c.95G>A​(p.Arg32Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,296 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

RNF32
NM_030936.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.955
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.046144962).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RNF32NM_030936.4 linkuse as main transcriptc.95G>A p.Arg32Gln missense_variant 3/9 ENST00000317955.10 NP_112198.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RNF32ENST00000317955.10 linkuse as main transcriptc.95G>A p.Arg32Gln missense_variant 3/91 NM_030936.4 ENSP00000315950 P1Q9H0A6-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1460296
Hom.:
0
Cov.:
30
AF XY:
0.00000275
AC XY:
2
AN XY:
726510
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
33

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 GeneticsDec 15, 2022The c.95G>A (p.R32Q) alteration is located in exon 3 (coding exon 2) of the RNF32 gene. This alteration results from a G to A substitution at nucleotide position 95, causing the arginine (R) at amino acid position 32 to be replaced by a glutamine (Q). 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
0.068
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
2.8
DANN
Benign
0.56
DEOGEN2
Benign
0.0041
.;T;T;T;.;T;.
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.016
N
LIST_S2
Benign
0.76
T;.;.;.;T;T;T
M_CAP
Uncertain
0.10
D
MetaRNN
Benign
0.046
T;T;T;T;T;T;T
MetaSVM
Benign
-0.65
T
MutationAssessor
Benign
0.24
.;N;N;N;.;N;N
MutationTaster
Benign
1.0
N;N;N;N;N;N;N;N
PrimateAI
Benign
0.18
T
PROVEAN
Benign
0.22
N;N;N;N;N;N;N
REVEL
Benign
0.12
Sift
Benign
0.69
T;T;T;T;T;T;T
Sift4G
Benign
0.67
T;T;T;T;T;T;T
Polyphen
0.0040, 0.011, 0.0050
.;B;B;B;B;B;B
Vest4
0.077, 0.13, 0.13, 0.11
MutPred
0.25
Gain of loop (P = 0.069);Gain of loop (P = 0.069);Gain of loop (P = 0.069);Gain of loop (P = 0.069);Gain of loop (P = 0.069);Gain of loop (P = 0.069);Gain of loop (P = 0.069);
MVP
0.53
MPC
0.18
ClinPred
0.022
T
GERP RS
-1.4
Varity_R
0.030
gMVP
0.11

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-156437272; COSMIC: COSV58731593; COSMIC: COSV58731593; API