4-153723406-C-A

Variant names:

• chr4-153723406-C-A
• rs1219355122
• NM_173662.4:c.454G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173662.4(RNF175):​c.454G>T​(p.Val152Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,456,698 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V152I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RNF175 NM_173662.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.893
• Publications: 0 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]

ENSG00000249309 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24112722).

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.454G>T	p.Val152Phe	missense	Exon 5 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.454G>T	p.Val152Phe	missense	Exon 5 of 9	ENSP00000340979.4	Q8N4F7-1
	RNF175	ENST00000955649.1		c.358G>T	p.Val120Phe	missense	Exon 5 of 9	ENSP00000625708.1
	RNF175	ENST00000897861.1		c.454G>T	p.Val152Phe	missense	Exon 5 of 8	ENSP00000567920.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1456698 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 724782

African (AFR) AF: 0.00 AC: 0 AN: 33392

American (AMR) AF: 0.00 AC: 0 AN: 44626

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26068

East Asian (EAS) AF: 0.00 AC: 0 AN: 39658

South Asian (SAS) AF: 0.00 AC: 0 AN: 85890

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53342

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1107754

Other (OTH) AF: 0.00 AC: 0 AN: 60206

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.029	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	20
DANN	Benign	0.90
DEOGEN2	Benign	0.038	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.89
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.20
Sift	Benign	0.088	T
Sift4G	Benign	0.11	T
Polyphen		0.10	B
Vest4		0.60
MutPred		0.34		Loss of helix (P = 0.028)
MVP		0.50
MPC		0.17
ClinPred		0.95	D
GERP RS		2.6
Varity_R		0.16
gMVP		0.87
Mutation Taster		=84/16	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: rs1219355122; hg19: chr4-154644558;