13-79366184-G-A

Position:

• chr13-79366184-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001366735.2(RBM26):​c.1147C>T​(p.Pro383Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RBM26 NM_001366735.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.60

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM26	NM_001366735.2	c.1147C>T	p.Pro383Ser	missense_variant	8/22	ENST00000438737.3	NP_001353664.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM26	ENST00000438737.3	c.1147C>T	p.Pro383Ser	missense_variant	8/22	5	NM_001366735.2	ENSP00000387531	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 17, 2024

The c.1147C>T (p.P383S) alteration is located in exon 8 (coding exon 8) of the RBM26 gene. This alteration results from a C to T substitution at nucleotide position 1147, causing the proline (P) at amino acid position 383 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Benign	0.0088	T
BayesDel_noAF	Benign	-0.23
CADD	Pathogenic	31
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.025	.;.;.;T
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.85
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D;D;D;D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.47	T;T;T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Uncertain	2.1	M;.;M;M
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.9	N;.;N;D
REVEL	Benign	0.26
Sift	Benign	0.071	T;.;T;D
Sift4G	Benign	0.20	T;T;T;T
Polyphen		1.0	D;.;D;D
Vest4		0.56
MutPred		0.22		Gain of phosphorylation at P383 (P = 0.0108);Gain of phosphorylation at P383 (P = 0.0108);Gain of phosphorylation at P383 (P = 0.0108);Gain of phosphorylation at P383 (P = 0.0108);
MVP		0.58
MPC		1.4
ClinPred		0.82	D
GERP RS		5.9
Varity_R		0.15
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2075252702; hg19: chr13-79940319; COSMIC: COSV57400062;