18-32018944-C-T

Variant names:

• chr18-32018944-C-T
• rs776932441
• NM_017831.4:c.81C>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 2P and 9B. PM2 BP4_Strong BP7 BS2

The NM_017831.4(RNF125):​c.81C>T​(p.Asp27Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,190 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: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: RNF125 NM_017831.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0100
• Publications: 0 publications found

Genes affected

RNF125 (HGNC:21150): (ring finger protein 125) This gene encodes a novel E3 ubiquitin ligase that contains a RING finger domain in the N-terminus and three zinc-binding and one ubiquitin-interacting motif in the C-terminus. As a result of myristoylation, this protein associates with membranes and is primarily localized to intracellular membrane systems. The encoded protein may function as a positive regulator in the T-cell receptor signaling pathway. [provided by RefSeq, Mar 2012]

RNF125 Gene-Disease associations (from GenCC):

• Tenorio syndrome

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

ENSG00000263917 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP7: Synonymous conserved (PhyloP=0.01 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF125	NM_017831.4	c.81C>T	p.Asp27Asp	synonymous_variant	Exon 1 of 6	ENST00000217740.4	NP_060301.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF125	ENST00000217740.4	c.81C>T	p.Asp27Asp	synonymous_variant	Exon 1 of 6	1	NM_017831.4	ENSP00000217740.3
RNF125	ENST00000718283.1	c.81C>T	p.Asp27Asp	synonymous_variant	Exon 1 of 6			ENSP00000520722.1
RNF125	ENST00000718284.1	c.81C>T	p.Asp27Asp	synonymous_variant	Exon 1 of 5			ENSP00000520723.1
ENSG00000263917	ENST00000583184.1	n.116C>T		non_coding_transcript_exon_variant	Exon 1 of 5	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461190 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726928

African (AFR) AF: 0.00 AC: 0 AN: 33438

American (AMR) AF: 0.00 AC: 0 AN: 44664

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26076

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.00 AC: 0 AN: 86146

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53298

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111780

Other (OTH) AF: 0.00 AC: 0 AN: 60352

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	6.1
DANN	Benign	0.94
PhyloP100		0.010
PromoterAI		-0.046	Neutral

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: rs776932441; hg19: chr18-29598907;