7-156654648-G-A

Variant names:

• chr7-156654648-G-A
• rs554840615
• NM_030936.4:c.347G>A

Variant summary

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

The NM_030936.4(RNF32):​c.347G>A​(p.Arg116His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000347 in 1,613,964 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000034 (0 hom.)
• Consequence: RNF32 NM_030936.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.66

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)

ACMG classification

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 rank	MANE	Protein	UniProt
RNF32	NM_030936.4	c.347G>A	p.Arg116His	missense_variant	Exon 4 of 9	ENST00000317955.10	NP_112198.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF32	ENST00000317955.10	c.347G>A	p.Arg116His	missense_variant	Exon 4 of 9	1	NM_030936.4	ENSP00000315950.5

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152162 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000756 AC: 19 AN: 251478 Hom.: 0 AF XY: 0.0000957 AC XY: 13 AN XY: 135912

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000868

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000217

Gnomad SAS exome AF: 0.000261

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000342 AC: 50 AN: 1461684 Hom.: 0 Cov.: 30 AF XY: 0.0000330 AC XY: 24 AN XY: 727174

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000671

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000202

Gnomad4 SAS exome AF: 0.000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000540

Gnomad4 OTH exome AF: 0.0000497

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152280 Hom.: 0 Cov.: 33 AF XY: 0.0000537 AC XY: 4 AN XY: 74464

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000675 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.0000906 AC: 11

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.347G>A (p.R116H) alteration is located in exon 4 (coding exon 3) of the RNF32 gene. This alteration results from a G to A substitution at nucleotide position 347, causing the arginine (R) at amino acid position 116 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	Benign	0.19
BayesDel_addAF	Uncertain	0.080	D
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.080	.;T;T;T;.;T;.
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.91	D;.;.;.;D;D;D
M_CAP	Uncertain	0.14	D
MetaRNN	Uncertain	0.57	D;D;D;D;D;D;D
MetaSVM	Pathogenic	0.89	D
MutationAssessor	Uncertain	2.8	.;M;M;M;.;M;M
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-3.4	D;D;D;D;D;D;D
REVEL	Uncertain	0.61
Sift	Uncertain	0.018	D;D;D;D;D;D;D
Sift4G	Uncertain	0.018	D;D;D;D;D;D;D
Polyphen		1.0, 1.0	.;D;D;D;D;D;D
Vest4		0.73, 0.75, 0.74, 0.78, 0.77
MutPred		0.38		Gain of catalytic residue at L118 (P = 0.0536);Gain of catalytic residue at L118 (P = 0.0536);Gain of catalytic residue at L118 (P = 0.0536);Gain of catalytic residue at L118 (P = 0.0536);Gain of catalytic residue at L118 (P = 0.0536);Gain of catalytic residue at L118 (P = 0.0536);Gain of catalytic residue at L118 (P = 0.0536);
MVP		0.96
MPC		0.67
ClinPred		0.81	D
GERP RS		5.3
Varity_R		0.33
gMVP		0.47

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

Other links and lift over

dbSNP: rs554840615; hg19: chr7-156447342;