12-116749868-G-A

Variant names:

• chr12-116749868-G-A
• rs761983753
• NM_001382266.1:c.111G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001382266.1(RNFT2):​c.111G>A​(p.Glu37Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000697 in 1,433,960 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: RNFT2 NM_001382266.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.57
• Publications: 0 publications found

Genes affected

RNFT2 (HGNC:25905): (ring finger protein, transmembrane 2) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in positive regulation of ERAD pathway and protein ubiquitination. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP7: Synonymous conserved (PhyloP=2.57 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382266.1. 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
	RNFT2	NM_001382266.1	MANE Select	c.111G>A	p.Glu37Glu	synonymous	Exon 4 of 11	NP_001369195.1	Q96EX2-1
	RNFT2	NM_001109903.2		c.111G>A	p.Glu37Glu	synonymous	Exon 4 of 12	NP_001103373.1	Q96EX2-1
	RNFT2	NM_032814.4		c.111G>A	p.Glu37Glu	synonymous	Exon 4 of 11	NP_116203.2	Q96EX2-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNFT2	ENST00000257575.9	TSL:5 MANE Select	c.111G>A	p.Glu37Glu	synonymous	Exon 4 of 11	ENSP00000257575.4	Q96EX2-1
	RNFT2	ENST00000392549.7	TSL:5	c.111G>A	p.Glu37Glu	synonymous	Exon 4 of 12	ENSP00000376332.2	Q96EX2-1
	RNFT2	ENST00000407967.7	TSL:5	c.111G>A	p.Glu37Glu	synonymous	Exon 4 of 11	ENSP00000385669.3	Q96EX2-5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.97e-7 AC: 1 AN: 1433960 Hom.: 0 Cov.: 32 AF XY: 0.00000141 AC XY: 1 AN XY: 710608

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32994

American (AMR) AF: 0.00 AC: 0 AN: 40332

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25600

East Asian (EAS) AF: 0.00 AC: 0 AN: 38418

South Asian (SAS) AF: 0.00 AC: 0 AN: 81962

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51490

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5734

European-Non Finnish (NFE) AF: 9.11e-7 AC: 1 AN: 1098100

Other (OTH) AF: 0.00 AC: 0 AN: 59330

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	9.1
DANN	Benign	0.35
PhyloP100		2.6

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: rs761983753; hg19: chr12-117187673;