rs1337

Variant names:

• chr4-153710435-C-A
• rs1337
• NM_173662.4:c.921G>T

Your query was ambiguous. Multiple possible variants found:

• chr4-153710435-C-A
• chr4-153710435-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_173662.4(RNF175):​c.921G>T​(p.Leu307Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RNF175 NM_173662.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.30
• Publications: 32 publications found

Genes affected

RNF175 (HGNC:27735): (ring finger protein 175) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in ubiquitin-dependent ERAD pathway. Predicted to be integral component of membrane. Predicted to be active in Golgi membrane and endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

TLR2 (HGNC:11848): (toll like receptor 2) The protein encoded by this gene is a member of the Toll-like receptor (TLR) family which plays a fundamental role in pathogen recognition and activation of innate immunity. TLRs are highly conserved from Drosophila to humans and share structural and functional similarities. This protein is a cell-surface protein that can form heterodimers with other TLR family members to recognize conserved molecules derived from microorganisms known as pathogen-associated molecular patterns (PAMPs). Activation of TLRs by PAMPs leads to an up-regulation of signaling pathways to modulate the host's inflammatory response. This gene is also thought to promote apoptosis in response to bacterial lipoproteins. This gene has been implicated in the pathogenesis of several autoimmune diseases. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41529894).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173662.4. 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
	RNF175	NM_173662.4	MANE Select	c.921G>T	p.Leu307Phe	missense	Exon 9 of 9	NP_775933.2	Q8N4F7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF175	ENST00000347063.9	TSL:1 MANE Select	c.921G>T	p.Leu307Phe	missense	Exon 9 of 9	ENSP00000340979.4	Q8N4F7-1
	RNF175	ENST00000955649.1		c.825G>T	p.Leu275Phe	missense	Exon 9 of 9	ENSP00000625708.1
	RNF175	ENST00000897861.1		c.819G>T	p.Leu273Phe	missense	Exon 8 of 8	ENSP00000567920.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1443610 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 716062

African (AFR) AF: 0.00 AC: 0 AN: 33220

American (AMR) AF: 0.00 AC: 0 AN: 42246

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25696

East Asian (EAS) AF: 0.00 AC: 0 AN: 39372

South Asian (SAS) AF: 0.00 AC: 0 AN: 82994

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52500

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1102056

Other (OTH) AF: 0.00 AC: 0 AN: 59768

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 2375

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.031	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.8	L
PhyloP100		1.3
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.23
Sift	Benign	0.12	T
Sift4G	Benign	0.18	T
Polyphen		0.98	D
Vest4		0.23
MutPred		0.50		Gain of helix (P = 0.0854)
MVP		0.38
MPC		0.27
ClinPred		0.86	D
GERP RS		2.5
Varity_R		0.13
gMVP		0.60
Mutation Taster		=92/8	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: rs1337; hg19: chr4-154631587;