7-156658170-T-C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_030936.4(RNF32):ā€‹c.493T>Cā€‹(p.Cys165Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,772 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

RNF32
NM_030936.4 missense

Scores

14
3
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.69
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)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.98

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RNF32NM_030936.4 linkuse as main transcriptc.493T>C p.Cys165Arg missense_variant 6/9 ENST00000317955.10 NP_112198.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RNF32ENST00000317955.10 linkuse as main transcriptc.493T>C p.Cys165Arg missense_variant 6/91 NM_030936.4 ENSP00000315950 P1Q9H0A6-1
RNF32-AS1ENST00000670834.1 linkuse as main transcriptn.1413A>G non_coding_transcript_exon_variant 1/3

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461772
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727208
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0

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 04, 2024The c.493T>C (p.C165R) alteration is located in exon 6 (coding exon 5) of the RNF32 gene. This alteration results from a T to C substitution at nucleotide position 493, causing the cysteine (C) at amino acid position 165 to be replaced by an arginine (R). 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
0.99
BayesDel_addAF
Pathogenic
0.56
D
BayesDel_noAF
Pathogenic
0.56
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Benign
0.26
.;T;T;T;.;T;.
Eigen
Pathogenic
0.94
Eigen_PC
Pathogenic
0.80
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Uncertain
0.93
D;.;.;.;D;D;D
M_CAP
Pathogenic
0.52
D
MetaRNN
Pathogenic
0.98
D;D;D;D;D;D;D
MetaSVM
Pathogenic
0.91
D
MutationAssessor
Pathogenic
5.2
.;H;H;H;.;H;H
MutationTaster
Benign
1.0
D;D;D;D;D;D;D
PrimateAI
Pathogenic
0.81
D
PROVEAN
Pathogenic
-11
D;D;D;D;D;D;D
REVEL
Pathogenic
0.95
Sift
Pathogenic
0.0
D;D;D;D;D;D;D
Sift4G
Pathogenic
0.0
D;D;D;D;D;D;D
Polyphen
1.0
.;D;D;D;D;D;D
Vest4
0.96, 0.98, 0.98
MutPred
0.86
Gain of MoRF binding (P = 9e-04);Gain of MoRF binding (P = 9e-04);Gain of MoRF binding (P = 9e-04);Gain of MoRF binding (P = 9e-04);Gain of MoRF binding (P = 9e-04);Gain of MoRF binding (P = 9e-04);Gain of MoRF binding (P = 9e-04);
MVP
0.98
MPC
0.89
ClinPred
1.0
D
GERP RS
4.8
Varity_R
0.97
gMVP
0.89

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: rs771084571; hg19: chr7-156450864; API