chr1-228487816-A-T

Variant names:

• chr1-228487816-A-T
• rs1463569095
• NM_001010858.3:c.328A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001010858.3(RNF187):​c.328A>T​(p.Met110Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000295 in 1,184,450 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M110V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000026 (0 hom.)
• Consequence: RNF187 NM_001010858.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0300
• Publications: 0 publications found

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]

ENSG00000293430 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03612247).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010858.3. 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
	RNF187	NM_001010858.3	MANE Select	c.328A>T	p.Met110Leu	missense	Exon 1 of 4	NP_001010858.2	Q5TA31

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF187	ENST00000305943.9	TSL:1 MANE Select	c.328A>T	p.Met110Leu	missense	Exon 1 of 4	ENSP00000306396.9	Q5TA31
	ENSG00000293430	ENST00000739614.1		n.658-6824T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000532 AC: 8 AN: 150362 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00203

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 5138 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000261 AC: 27 AN: 1034088 Hom.: 0 Cov.: 30 AF XY: 0.0000365 AC XY: 18 AN XY: 492936

African (AFR) AF: 0.00 AC: 0 AN: 20414

American (AMR) AF: 0.00 AC: 0 AN: 6758

Ashkenazi Jewish (ASJ) AF: 0.00161 AC: 19 AN: 11780

East Asian (EAS) AF: 0.00 AC: 0 AN: 20242

South Asian (SAS) AF: 0.00 AC: 0 AN: 27626

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 17826

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2582

European-Non Finnish (NFE) AF: 0.00000563 AC: 5 AN: 887912

Other (OTH) AF: 0.0000770 AC: 3 AN: 38948

GnomAD4 genome AF: 0.0000532 AC: 8 AN: 150362 Hom.: 0 Cov.: 32 AF XY: 0.0000681 AC XY: 5 AN XY: 73372

African (AFR) AF: 0.00 AC: 0 AN: 41158

American (AMR) AF: 0.00 AC: 0 AN: 15130

Ashkenazi Jewish (ASJ) AF: 0.00203 AC: 7 AN: 3450

East Asian (EAS) AF: 0.00 AC: 0 AN: 5094

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10010

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67416

Other (OTH) AF: 0.00 AC: 0 AN: 2062

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000680

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	7.8
DANN	Benign	0.50
DEOGEN2	Benign	0.010	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.038	N
M_CAP	Uncertain	0.098	D
MetaRNN	Benign	0.036	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.030
PrimateAI	Pathogenic	0.90	D
REVEL	Benign	0.028
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.22
MutPred		0.29		Loss of methylation at R109 (P = 0.1195)
MVP		0.23
ClinPred		0.026	T
GERP RS		0.68
PromoterAI		-0.12	Neutral
Varity_R		0.11
gMVP		0.18
Mutation Taster		=146/54	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: rs1463569095; hg19: chr1-228675517;