7-156658494-G-A

Variant names:

• chr7-156658494-G-A
• rs970450561
• NM_030936.4:c.608G>A

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_030936.4(RNF32):​c.608G>A​(p.Arg203Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,346 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R203T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RNF32 NM_030936.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.29
• Publications: 0 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.94

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.608G>A	p.Arg203Lys	missense	Exon 7 of 9	NP_112198.1	Q9H0A6-1
	RNF32	NM_001184996.2		c.608G>A	p.Arg203Lys	missense	Exon 7 of 9	NP_001171925.1	Q9H0A6-1
	RNF32	NM_001184997.1		c.608G>A	p.Arg203Lys	missense	Exon 7 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.608G>A	p.Arg203Lys	missense	Exon 7 of 9	ENSP00000315950.5	Q9H0A6-1
	RNF32	ENST00000392743.6	TSL:1	c.608G>A	p.Arg203Lys	missense	Exon 7 of 9	ENSP00000376499.2	Q9H0A6-1
	RNF32	ENST00000432459.6	TSL:1	c.608G>A	p.Arg203Lys	missense	Exon 7 of 9	ENSP00000405588.2	Q9H0A6-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461346 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727034

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111518

Other (OTH) AF: 0.00 AC: 0 AN: 60370

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.074	D
MetaRNN	Pathogenic	0.94	D
MetaSVM	Uncertain	0.12	D
MutationAssessor	Pathogenic	3.0	M
PhyloP100		4.3
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.51
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.049	D
Polyphen		1.0	D
Vest4		0.33
MutPred		0.87		Gain of methylation at R203 (P = 0.0472)
MVP		0.87
MPC		0.66
ClinPred		0.99	D
GERP RS		4.8
Varity_R		0.82
gMVP		0.75
Mutation Taster		=65/35	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: rs970450561; hg19: chr7-156451188;