chr19-648436-C-G

Variant names:

• chr19-648436-C-G
• rs528146502
• NM_194460.3:c.722G>C

Variant summary

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

The NM_194460.3(RNF126):​c.722G>C​(p.Arg241Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,438,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R241H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RNF126 NM_194460.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.311
• Publications: 0 publications found

Genes affected

RNF126 (HGNC:21151): (ring finger protein 126) The protein encoded by this gene contains a RING finger domain, a motif present in a variety of functionally distinct proteins and known to be involved in protein-protein and protein-DNA interactions. [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=0.09554553).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF126	NM_194460.3	c.722G>C	p.Arg241Pro	missense_variant	Exon 8 of 9	ENST00000292363.10	NP_919442.1
RNF126	NM_001366018.1	c.641G>C	p.Arg214Pro	missense_variant	Exon 8 of 9		NP_001352947.1
RNF126	XM_047439069.1	c.*52G>C		3_prime_UTR_variant	Exon 8 of 8		XP_047295025.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF126	ENST00000292363.10	c.722G>C	p.Arg241Pro	missense_variant	Exon 8 of 9	1	NM_194460.3	ENSP00000292363.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1438876 Hom.: 0 Cov.: 35 AF XY: 0.00000140 AC XY: 1 AN XY: 714492

African (AFR) AF: 0.00 AC: 0 AN: 32818

American (AMR) AF: 0.00 AC: 0 AN: 43038

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25850

East Asian (EAS) AF: 0.00 AC: 0 AN: 38374

South Asian (SAS) AF: 0.00 AC: 0 AN: 83136

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47926

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4184

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1104100

Other (OTH) AF: 0.00 AC: 0 AN: 59450

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	9.8
DANN	Benign	0.82
DEOGEN2	Benign	0.027	T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.16	N
LIST_S2	Uncertain	0.88	D;D
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.096	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.74	N;.
PhyloP100		-0.31
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.51	N;.
REVEL	Benign	0.018
Sift	Benign	0.38	T;.
Sift4G	Benign	0.50	T;.
Vest4		0.47
MutPred		0.54		Gain of catalytic residue at R241 (P = 0.1545);.;
MVP		0.21
MPC		0.36
ClinPred		0.065	T
GERP RS		-0.92
Varity_R		0.10
Mutation Taster		=78/22	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: rs528146502; hg19: chr19-648436;