NM_005778.4:c.2037T>C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005778.4(RBM5):​c.2037T>C​(p.Tyr679Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 1,612,388 control chromosomes in the GnomAD database, including 307,161 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.65 (33139 hom., cov: 32)
  • Exomes 𝑓: 0.61 (274022 hom.)
• Consequence: RBM5 NM_005778.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0300

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM5	NM_005778.4	c.2037T>C	p.Tyr679Tyr	synonymous_variant	Exon 22 of 25	ENST00000347869.8	NP_005769.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM5	ENST00000347869.8	c.2037T>C	p.Tyr679Tyr	synonymous_variant	Exon 22 of 25	1	NM_005778.4	ENSP00000343054.3

Frequencies

GnomAD3 genomes AF: 0.654 AC: 99339 AN: 151984 Hom.: 33093 Cov.: 32

Gnomad AFR AF: 0.729

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.678

Gnomad ASJ AF: 0.741

Gnomad EAS AF: 0.885

Gnomad SAS AF: 0.829

Gnomad FIN AF: 0.618

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.640

GnomAD3 exomes AF: 0.675 AC: 169668 AN: 251410 Hom.: 58931 AF XY: 0.673 AC XY: 91475 AN XY: 135890

Gnomad AFR exome AF: 0.726

Gnomad AMR exome AF: 0.761

Gnomad ASJ exome AF: 0.735

Gnomad EAS exome AF: 0.884

Gnomad SAS exome AF: 0.827

Gnomad FIN exome AF: 0.621

Gnomad NFE exome AF: 0.573

Gnomad OTH exome AF: 0.636

GnomAD4 exome AF: 0.606 AC: 884777 AN: 1460286 Hom.: 274022 Cov.: 45 AF XY: 0.611 AC XY: 443722 AN XY: 726532

Gnomad4 AFR exome AF: 0.733

Gnomad4 AMR exome AF: 0.752

Gnomad4 ASJ exome AF: 0.733

Gnomad4 EAS exome AF: 0.871

Gnomad4 SAS exome AF: 0.822

Gnomad4 FIN exome AF: 0.617

Gnomad4 NFE exome AF: 0.565

Gnomad4 OTH exome AF: 0.624

GnomAD4 genome AF: 0.654 AC: 99438 AN: 152102 Hom.: 33139 Cov.: 32 AF XY: 0.662 AC XY: 49198 AN XY: 74328

Gnomad4 AFR AF: 0.729

Gnomad4 AMR AF: 0.679

Gnomad4 ASJ AF: 0.741

Gnomad4 EAS AF: 0.886

Gnomad4 SAS AF: 0.829

Gnomad4 FIN AF: 0.618

Gnomad4 NFE AF: 0.575

Gnomad4 OTH AF: 0.637

Alfa AF: 0.601 Hom.: 47281

Bravo AF: 0.655

Asia WGS AF: 0.799 AC: 2778 AN: 3478

EpiCase AF: 0.581

EpiControl AF: 0.578

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	7.6
DANN	Benign	0.80

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

Publications

LitVar

Other links and lift over

dbSNP: rs1138536; hg19: chr3-50153356;