1-6209287-G-C

Variant names:

• chr1-6209287-G-C
• rs567614508
• NM_207396.3:c.571G>C

Variant summary

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

The NM_207396.3(RNF207):​c.571G>C​(p.Val191Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000215 in 1,396,476 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. V191M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: RNF207 NM_207396.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.41
• Publications: 0 publications found

Genes affected

RNF207 (HGNC:32947): (ring finger protein 207) Enables Hsp70 protein binding activity; chaperone binding activity; and transmembrane transporter binding activity. Involved in positive regulation of delayed rectifier potassium channel activity; positive regulation of gene expression; and positive regulation of voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization. Located in perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

RPL22 (HGNC:10315): (ribosomal protein L22) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a cytoplasmic ribosomal protein that is a component of the 60S subunit. The protein belongs to the L22E family of ribosomal proteins. Its initiating methionine residue is post-translationally removed. The protein can bind specifically to Epstein-Barr virus-encoded RNAs (EBERs) 1 and 2. The mouse protein has been shown to be capable of binding to heparin. Transcript variants utilizing alternative polyA signals exist. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. It was previously thought that this gene mapped to 3q26 and that it was fused to the acute myeloid leukemia 1 (AML1) gene located at 21q22 in some therapy-related myelodysplastic syndrome patients with 3;21 translocations; however, these fusions actually involve a ribosomal protein L22 pseudogene located at 3q26, and this gene actually maps to 1p36.3-p36.2. [provided by RefSeq, Jul 2008]

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=0.124127656).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207396.3. 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
	RNF207	NM_207396.3	MANE Select	c.571G>C	p.Val191Leu	missense	Exon 6 of 18	NP_997279.2	Q6ZRF8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF207	ENST00000377939.5	TSL:5 MANE Select	c.571G>C	p.Val191Leu	missense	Exon 6 of 18	ENSP00000367173.4	Q6ZRF8-1
	RNF207	ENST00000485539.5	TSL:1	n.510G>C		non_coding_transcript_exon	Exon 3 of 6
	RNF207	ENST00000951272.1		c.571G>C	p.Val191Leu	missense	Exon 6 of 20	ENSP00000621331.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000695 AC: 1 AN: 143902 AF XY: 0.0000129

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: 0.00000215 AC: 3 AN: 1396476 Hom.: 0 Cov.: 35 AF XY: 0.00000290 AC XY: 2 AN XY: 688834

African (AFR) AF: 0.00 AC: 0 AN: 31576

American (AMR) AF: 0.00 AC: 0 AN: 35716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25138

East Asian (EAS) AF: 0.00 AC: 0 AN: 35764

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79208

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46968

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5504

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078678

Other (OTH) AF: 0.0000173 AC: 1 AN: 57924

GnomAD4 genome Cov.: 33

ExAC AF: 0.0000117 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0064	T
Eigen	Benign	-0.062
Eigen_PC	Benign	0.098
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		4.4
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.098
Sift	Benign	0.10	T
Sift4G	Uncertain	0.020	D
Polyphen		0.072	B
Vest4		0.14
MutPred		0.40		Gain of helix (P = 0.0325)
MVP		0.38
MPC		0.26
ClinPred		0.34	T
GERP RS		3.3
PromoterAI		0.12	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.14
gMVP		0.34
Mutation Taster		=74/26	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs567614508; hg19: chr1-6269347;