rs1138536

Variant names:

• chr3-50115923-T-A
• rs1138536
• NM_005778.4:c.2037T>A

Your query was ambiguous. Multiple possible variants found:

• chr3-50115923-T-A
• chr3-50115923-T-C

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_005778.4(RBM5):​c.2037T>A​(p.Tyr679*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RBM5 NM_005778.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0300
• Publications: 43 publications found

Genes affected

RBM5 (HGNC:9902): (RNA binding motif protein 5) This gene is a candidate tumor suppressor gene which encodes a nuclear RNA binding protein that is a component of the spliceosome A complex. The encoded protein plays a role in the induction of cell cycle arrest and apoptosis through pre-mRNA splicing of multiple target genes including the tumor suppressor protein p53. This gene is located within the tumor suppressor region 3p21.3, and may play a role in the inhibition of tumor transformation and progression of several malignancies including lung cancer. [provided by RefSeq, Oct 2011]

SEMA3F-AS1 (HGNC:40518): (SEMA3F antisense RNA 1)

ACMG classification

Our verdict: Pathogenic. The variant received 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005778.4. 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
	RBM5	NM_005778.4	MANE Select	c.2037T>A	p.Tyr679*	stop_gained	Exon 22 of 25	NP_005769.1
	RBM5	NR_036627.3		n.2127T>A		non_coding_transcript_exon	Exon 21 of 24
	SEMA3F-AS1	NR_135301.1		n.*99A>T		downstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM5	ENST00000347869.8	TSL:1 MANE Select	c.2037T>A	p.Tyr679*	stop_gained	Exon 22 of 25	ENSP00000343054.3
	RBM5	ENST00000852698.1		c.2037T>A	p.Tyr679*	stop_gained	Exon 22 of 26	ENSP00000522757.1
	RBM5	ENST00000852694.1		c.2043T>A	p.Tyr681*	stop_gained	Exon 22 of 25	ENSP00000522753.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 45

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.52	D
BayesDel_noAF	Pathogenic	0.51
CADD	Pathogenic	36
DANN	Uncertain	0.99
Eigen	Uncertain	0.29
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.87	D
PhyloP100		0.030
Vest4		0.92
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=1/199	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs1138536; hg19: chr3-50153356;