7-156675706-T-C

Position:

• chr7-156675706-T-C

Variant summary

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

The NM_030936.4(RNF32):​c.695T>C​(p.Ile232Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 4.90

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 (HGNC:):

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/exons	MANE	Protein	UniProt
RNF32	NM_030936.4	c.695T>C	p.Ile232Thr	missense_variant	8/9	ENST00000317955.10	NP_112198.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF32	ENST00000317955.10	c.695T>C	p.Ile232Thr	missense_variant	8/9	1	NM_030936.4	ENSP00000315950.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

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

Jun 16, 2024

The c.695T>C (p.I232T) alteration is located in exon 8 (coding exon 7) of the RNF32 gene. This alteration results from a T to C substitution at nucleotide position 695, causing the isoleucine (I) at amino acid position 232 to be replaced by a threonine (T). 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	0.72
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.099	T;T;T;.;T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.81	.;.;.;T;T
M_CAP	Benign	0.0062	T
MetaRNN	Uncertain	0.56	D;D;D;D;D
MetaSVM	Benign	-0.96	T
MutationAssessor	Pathogenic	2.9	M;M;M;.;M
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-2.8	D;D;D;D;D
REVEL	Benign	0.21
Sift	Uncertain	0.017	D;D;D;D;D
Sift4G	Benign	0.13	T;T;T;D;T
Polyphen		0.77	P;P;P;B;P
Vest4		0.77
MutPred		0.53		Loss of catalytic residue at I232 (P = 0.0043);Loss of catalytic residue at I232 (P = 0.0043);Loss of catalytic residue at I232 (P = 0.0043);Loss of catalytic residue at I232 (P = 0.0043);Loss of catalytic residue at I232 (P = 0.0043);
MVP		0.56
MPC		0.38
ClinPred		0.98	D
GERP RS		5.2
Varity_R		0.27
gMVP		0.43

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-156468400;