7-156654714-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_030936.4(RNF32):​c.413C>T​(p.Pro138Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000991 in 1,613,736 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

RNF32
NM_030936.4 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.32
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 Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RNF32NM_030936.4 linkuse as main transcriptc.413C>T p.Pro138Leu 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.413C>T p.Pro138Leu missense_variant 4/91 NM_030936.4 ENSP00000315950 P1Q9H0A6-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152208
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251330
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135844
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
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:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000103
AC:
15
AN:
1461528
Hom.:
0
Cov.:
31
AF XY:
0.00000688
AC XY:
5
AN XY:
727080
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:
0.0000135
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152208
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74364
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
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 GeneticsMay 31, 2023The c.413C>T (p.P138L) alteration is located in exon 4 (coding exon 3) of the RNF32 gene. This alteration results from a C to T substitution at nucleotide position 413, causing the proline (P) at amino acid position 138 to be replaced by a leucine (L). 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
0.27
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.41
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.050
.;T;T;T;.;T;.
Eigen
Benign
-0.23
Eigen_PC
Benign
-0.12
FATHMM_MKL
Benign
0.57
D
LIST_S2
Uncertain
0.95
D;.;.;.;D;D;D
M_CAP
Benign
0.016
T
MetaRNN
Uncertain
0.61
D;D;D;D;D;D;D
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.52
.;N;N;N;.;N;N
MutationTaster
Benign
1.0
D;D;D;D;D;D;D
PrimateAI
Benign
0.46
T
PROVEAN
Uncertain
-4.0
D;D;D;D;D;D;D
REVEL
Benign
0.22
Sift
Benign
0.22
T;T;T;T;T;T;T
Sift4G
Uncertain
0.017
D;D;D;D;D;D;D
Polyphen
0.035, 0.077, 0.0040
.;B;B;B;B;B;B
Vest4
0.59, 0.58, 0.58, 0.56, 0.52
MutPred
0.77
Loss of disorder (P = 0.0448);Loss of disorder (P = 0.0448);Loss of disorder (P = 0.0448);Loss of disorder (P = 0.0448);Loss of disorder (P = 0.0448);Loss of disorder (P = 0.0448);Loss of disorder (P = 0.0448);
MVP
0.71
MPC
0.19
ClinPred
0.90
D
GERP RS
5.3
Varity_R
0.21
gMVP
0.41

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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: rs767150856; hg19: chr7-156447408; API