7-156658502-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_030936.4(RNF32):ā€‹c.616T>Cā€‹(p.Tyr206His) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,126 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: š‘“ 0.0000066 ( 0 hom., cov: 33)

Consequence

RNF32
NM_030936.4 missense

Scores

7
6
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.39
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 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.823

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RNF32NM_030936.4 linkuse as main transcriptc.616T>C p.Tyr206His missense_variant 7/9 ENST00000317955.10 NP_112198.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RNF32ENST00000317955.10 linkuse as main transcriptc.616T>C p.Tyr206His missense_variant 7/91 NM_030936.4 ENSP00000315950 P1Q9H0A6-1
RNF32-AS1ENST00000670834.1 linkuse as main transcriptn.1081A>G non_coding_transcript_exon_variant 1/3

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152126
Hom.:
0
Cov.:
33
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
GnomAD4 exome
Cov.:
30
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152126
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74304
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:
0.0000712
Hom.:
0
Bravo
AF:
0.00000378

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 GeneticsMar 01, 2023The c.616T>C (p.Y206H) alteration is located in exon 7 (coding exon 6) of the RNF32 gene. This alteration results from a T to C substitution at nucleotide position 616, causing the tyrosine (Y) at amino acid position 206 to be replaced by a histidine (H). 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
0.85
BayesDel_addAF
Benign
0.0015
T
BayesDel_noAF
Benign
-0.24
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.15
.;T;T;T;.;T;.
Eigen
Pathogenic
0.70
Eigen_PC
Uncertain
0.61
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Uncertain
0.90
D;.;.;.;D;D;D
M_CAP
Benign
0.036
D
MetaRNN
Pathogenic
0.82
D;D;D;D;D;D;D
MetaSVM
Benign
-0.46
T
MutationAssessor
Pathogenic
3.0
.;M;M;M;.;M;M
MutationTaster
Benign
1.0
D;D;D;D;D;D;D
PrimateAI
Uncertain
0.57
T
PROVEAN
Pathogenic
-4.6
D;D;D;D;D;D;D
REVEL
Uncertain
0.50
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
0.56, 0.73, 0.73, 0.74, 0.71
MutPred
0.74
Gain of disorder (P = 0.0408);Gain of disorder (P = 0.0408);Gain of disorder (P = 0.0408);Gain of disorder (P = 0.0408);Gain of disorder (P = 0.0408);Gain of disorder (P = 0.0408);Gain of disorder (P = 0.0408);
MVP
0.67
MPC
0.75
ClinPred
1.0
D
GERP RS
4.8
Varity_R
0.80
gMVP
0.71

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: rs1391808816; hg19: chr7-156451196; API