1-228487556-T-G

Position:

• chr1-228487556-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001010858.3(RNF187):​c.68T>G​(p.Val23Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RNF187 NM_001010858.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.03

Genes affected

RNF187 (HGNC:27146): (ring finger protein 187) Enables ubiquitin-protein transferase activity. Involved in positive regulation of transcription, DNA-templated; proteasome-mediated ubiquitin-dependent protein catabolic process; and protein ubiquitination. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF187	NM_001010858.3	c.68T>G	p.Val23Gly	missense_variant	1/4	ENST00000305943.9	NP_001010858.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF187	ENST00000305943.9	c.68T>G	p.Val23Gly	missense_variant	1/4	1	NM_001010858.3	ENSP00000306396	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1092800 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 533470

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

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 27, 2021

The c.68T>G (p.V23G) alteration is located in exon 1 (coding exon 1) of the RNF187 gene. This alteration results from a T to G substitution at nucleotide position 68, causing the valine (V) at amino acid position 23 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	25
DANN	Benign	0.85
DEOGEN2	Uncertain	0.78	.;D
FATHMM_MKL	Benign	0.47	N
MetaRNN	Uncertain	0.51	D;D
MutationAssessor	Pathogenic	3.6	.;H
MutationTaster	Benign	0.99	D
PrimateAI	Pathogenic	0.94	D
Sift4G	Pathogenic	0.0	D;.
Polyphen		0.99	.;D
Vest4		0.46
MVP		0.76
GERP RS		3.4
Varity_R		0.17
gMVP		0.46

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-228675257;