chr7-156654647-C-T

Variant names:

• chr7-156654647-C-T
• rs200622568
• NM_030936.4:c.346C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_030936.4(RNF32):​c.346C>T​(p.Arg116Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000031 in 1,613,998 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R116H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000028 (0 hom.)
• Consequence: RNF32 NM_030936.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.01
• Publications: 2 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030936.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF32	NM_030936.4	MANE Select	c.346C>T	p.Arg116Cys	missense	Exon 4 of 9	NP_112198.1	Q9H0A6-1
	RNF32	NM_001184996.2		c.346C>T	p.Arg116Cys	missense	Exon 4 of 9	NP_001171925.1	Q9H0A6-1
	RNF32	NM_001184997.1		c.346C>T	p.Arg116Cys	missense	Exon 4 of 9	NP_001171926.1	Q9H0A6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF32	ENST00000317955.10	TSL:1 MANE Select	c.346C>T	p.Arg116Cys	missense	Exon 4 of 9	ENSP00000315950.5	Q9H0A6-1
	RNF32	ENST00000392743.6	TSL:1	c.346C>T	p.Arg116Cys	missense	Exon 4 of 9	ENSP00000376499.2	Q9H0A6-1
	RNF32	ENST00000432459.6	TSL:1	c.346C>T	p.Arg116Cys	missense	Exon 4 of 9	ENSP00000405588.2	Q9H0A6-1

Frequencies

GnomAD3 genomes AF: 0.0000591 AC: 9 AN: 152188 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

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: 0.000103

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000318 AC: 8 AN: 251470 AF XY: 0.0000515

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000615

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000280 AC: 41 AN: 1461692 Hom.: 0 Cov.: 31 AF XY: 0.0000303 AC XY: 22 AN XY: 727168

African (AFR) AF: 0.000149 AC: 5 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.0000252 AC: 28 AN: 1111832

Other (OTH) AF: 0.0000166 AC: 1 AN: 60390

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152306 Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3 AN XY: 74484

African (AFR) AF: 0.0000481 AC: 2 AN: 41554

American (AMR) AF: 0.00 AC: 0 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000348 Hom.: 0

Bravo AF: 0.0000491

ExAC AF: 0.0000412 AC: 5

EpiCase AF: 0.000218

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Pathogenic	0.28
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Benign	0.017
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.48	N
LIST_S2	Uncertain	0.93	D
M_CAP	Uncertain	0.18	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Uncertain	0.77	D
MutationAssessor	Uncertain	2.8	M
PhyloP100		2.0
PrimateAI	Uncertain	0.62	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Uncertain	0.64
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.79
MVP		0.90
MPC		0.70
ClinPred		0.94	D
GERP RS		1.6
Varity_R		0.54
gMVP		0.55
Mutation Taster		=58/42	polymorphism

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

Other links and lift over

dbSNP: rs200622568; hg19: chr7-156447341;