13-79322443-C-G

Variant names:

• chr13-79322443-C-G
• rs758507264
• NM_001366735.2:c.2840G>C

Variant summary

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

The NM_001366735.2(RBM26):​c.2840G>C​(p.Arg947Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000706 in 1,416,888 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R947H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: RBM26 NM_001366735.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.18
• 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: Uncertain_significance. The variant received 2 ACMG points.

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

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.2840G>C	p.Arg947Pro	missense	Exon 21 of 22	NP_001353664.1	Q5T8P6-1
	RBM26	NM_001286631.2		c.2846G>C	p.Arg949Pro	missense	Exon 21 of 22	NP_001273560.1	A0A087X0H9
	RBM26	NM_001286632.2		c.2768G>C	p.Arg923Pro	missense	Exon 20 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.2840G>C	p.Arg947Pro	missense	Exon 21 of 22	ENSP00000387531.2	Q5T8P6-1
	RBM26	ENST00000438724.5	TSL:1	c.2768G>C	p.Arg923Pro	missense	Exon 20 of 21	ENSP00000390222.1	Q5T8P6-2
	RBM26	ENST00000267229.11	TSL:1	c.2759G>C	p.Arg920Pro	missense	Exon 20 of 21	ENSP00000267229.7	Q5T8P6-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.06e-7 AC: 1 AN: 1416888 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 703972

African (AFR) AF: 0.00 AC: 0 AN: 30094

American (AMR) AF: 0.00 AC: 0 AN: 35072

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 36692

South Asian (SAS) AF: 0.00 AC: 0 AN: 77562

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52974

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5658

European-Non Finnish (NFE) AF: 9.13e-7 AC: 1 AN: 1095140

Other (OTH) AF: 0.00 AC: 0 AN: 58558

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Uncertain	0.092	D
BayesDel_noAF	Benign	-0.10
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.020	T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.7	L
PhyloP100		3.2
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.23
Sift	Benign	0.055	T
Sift4G	Uncertain	0.028	D
Polyphen		1.0	D
Vest4		0.74
MutPred		0.46		Loss of MoRF binding (P = 0.0012)
MVP		0.51
MPC		1.6
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.56
gMVP		0.81
Mutation Taster		=74/26	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: rs758507264; hg19: chr13-79896578;