4-1093539-GAC-G

Position:

• chr4-1093539-GAC-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001193318.3(RNF212):​c.720_721delGT​(p.Arg240fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000391 in 1,531,436 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00039 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00039 (2 hom.)
• Consequence: RNF212 NM_001193318.3 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.389

Genes affected

RNF212 (HGNC:27729): (ring finger protein 212) This gene encodes a RING finger protein that may function as a ubiquitin ligase. The encoded protein may be involved in meiotic recombination. This gene is located within a linkage disequilibrium block and polymorphisms in this gene may influence recombination rates. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Oct 2010]

RNF212 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF212	NM_001131034.4	c.247-2703_247-2702delGT		intron_variant		ENST00000433731.7	NP_001124506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF212	ENST00000433731.7	c.247-2703_247-2702delGT		intron_variant		1	NM_001131034.4	ENSP00000389709.2

Frequencies

GnomAD3 genomes AF: 0.000395 AC: 60 AN: 151764 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000726

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00405

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000280

Gnomad OTH AF: 0.00144

GnomAD4 exome AF: 0.000391 AC: 540 AN: 1379554 Hom.: 2 AF XY: 0.000432 AC XY: 294 AN XY: 680510

Gnomad4 AFR exome AF: 0.000480

Gnomad4 AMR exome AF: 0.000845

Gnomad4 ASJ exome AF: 0.00458

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000165

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000265

Gnomad4 OTH exome AF: 0.00102

GnomAD4 genome AF: 0.000388 AC: 59 AN: 151882 Hom.: 0 Cov.: 0 AF XY: 0.000445 AC XY: 33 AN XY: 74188

Gnomad4 AFR AF: 0.0000724

Gnomad4 AMR AF: 0.00111

Gnomad4 ASJ AF: 0.00405

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000280

Gnomad4 OTH AF: 0.00143

Alfa AF: 0.00933 Hom.: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Non-obstructive azoospermia Uncertain:1

Uncertain significance, criteria provided, single submitter

research

Institute of Reproductive Genetics, University of Münster

Mar 16, 2022

Variant found in homozygosis in an unaffected male. -

Computational scores

Source: dbNSFP v4.3

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: rs1491194367; hg19: chr4-1087327;