chr13-79358348-C-T

Variant names:

• chr13-79358348-C-T
• rs962778110
• NM_001366735.2:c.1615G>A

Variant summary

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

The NM_001366735.2(RBM26):​c.1615G>A​(p.Val539Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,611,960 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. V539L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RBM26 NM_001366735.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.98
• Publications: 0 publications found

Genes affected

RBM26 (HGNC:20327): (RNA binding motif protein 26) Enables RNA binding activity. Predicted to be involved in mRNA processing. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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=0.036254704).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366735.2. 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
	RBM26	NM_001366735.2	MANE Select	c.1615G>A	p.Val539Ile	missense	Exon 11 of 22	NP_001353664.1	Q5T8P6-1
	RBM26	NM_001286631.2		c.1630G>A	p.Val544Ile	missense	Exon 11 of 22	NP_001273560.1	A0A087X0H9
	RBM26	NM_001286632.2		c.1615G>A	p.Val539Ile	missense	Exon 11 of 21	NP_001273561.1	Q5T8P6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM26	ENST00000438737.3	TSL:5 MANE Select	c.1615G>A	p.Val539Ile	missense	Exon 11 of 22	ENSP00000387531.2	Q5T8P6-1
	RBM26	ENST00000438724.5	TSL:1	c.1615G>A	p.Val539Ile	missense	Exon 11 of 21	ENSP00000390222.1	Q5T8P6-2
	RBM26	ENST00000267229.11	TSL:1	c.1615G>A	p.Val539Ile	missense	Exon 11 of 21	ENSP00000267229.7	Q5T8P6-3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152154 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459806 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726114

African (AFR) AF: 0.0000299 AC: 1 AN: 33396

American (AMR) AF: 0.00 AC: 0 AN: 44388

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39534

South Asian (SAS) AF: 0.00 AC: 0 AN: 85680

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111214

Other (OTH) AF: 0.0000166 AC: 1 AN: 60336

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152154 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74334

African (AFR) AF: 0.0000241 AC: 1 AN: 41428

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	18
DANN	Benign	0.25
DEOGEN2	Benign	0.070	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.033
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.036	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	-1.6	N
PhyloP100		3.0
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	0.25	N
REVEL	Benign	0.075
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.013	B
Vest4		0.21
MutPred		0.41		Gain of helix (P = 0.0022)
MVP		0.22
MPC		0.38
ClinPred		0.53	D
GERP RS		4.3
Varity_R		0.036
gMVP		0.21
Mutation Taster		=90/10	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: rs962778110; hg19: chr13-79932483;