chr7-156654688-C-G

Position:

• chr7-156654688-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_030936.4(RNF32):​c.387C>G​(p.Ile129Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RNF32 NM_030936.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.433

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.845

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF32	NM_030936.4	c.387C>G	p.Ile129Met	missense_variant	4/9	ENST00000317955.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF32	ENST00000317955.10	c.387C>G	p.Ile129Met	missense_variant	4/9	1	NM_030936.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 04, 2021

The c.387C>G (p.I129M) alteration is located in exon 4 (coding exon 3) of the RNF32 gene. This alteration results from a C to G substitution at nucleotide position 387, causing the isoleucine (I) at amino acid position 129 to be replaced by a methionine (M). 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	0.80
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.26
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	.;T;T;T;.;T;.
Eigen	Benign	0.057
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.85	T;.;.;.;T;T;D
M_CAP	Benign	0.077	D
MetaRNN	Pathogenic	0.84	D;D;D;D;D;D;D
MetaSVM	Uncertain	0.61	D
MutationAssessor	Pathogenic	3.5	.;M;M;M;.;M;M
MutationTaster	Benign	1.0	D;D;D;D;D;D;D
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-2.8	D;D;D;D;D;D;D
REVEL	Pathogenic	0.70
Sift	Pathogenic	0.0	D;D;D;D;D;D;D
Sift4G	Uncertain	0.0020	D;D;D;D;D;D;D
Polyphen		1.0, 0.99	.;D;D;D;D;D;D
Vest4		0.80, 0.81, 0.81
MutPred		0.81		Gain of disorder (P = 0.0341);Gain of disorder (P = 0.0341);Gain of disorder (P = 0.0341);Gain of disorder (P = 0.0341);Gain of disorder (P = 0.0341);Gain of disorder (P = 0.0341);Gain of disorder (P = 0.0341);
MVP		0.77
MPC		0.62
ClinPred		0.99	D
GERP RS		-2.3
Varity_R		0.78
gMVP		0.68

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

LitVar

Other links and lift over

dbSNP: rs1799329074; hg19: chr7-156447382;