rs1337

Positions:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF175	NM_173662.4	c.921G>T	p.Leu307Phe	missense_variant	9/9	ENST00000347063.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF175	ENST00000347063.9	c.921G>T	p.Leu307Phe	missense_variant	9/9	1	NM_173662.4	P1

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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
MutationTaster	Benign	0.00027	P
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

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: rs1337; hg19: chr4-154631587;