1-235131924-C-A

Position:

• chr1-235131924-C-A

Variant summary

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

The ENST00000408888.8(RBM34):​c.1082G>T​(p.Arg361Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,460,740 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: RBM34 ENST00000408888.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.03

Genes affected

RBM34 (HGNC:28965): (RNA binding motif protein 34) This gene encodes a member of the RNA-binding motif family of RNA recognition motif proteins. The encoded protein contains an RNA-binding domain made up of two RNA recognition motif subdomains referred to as RNA recognition motif-1 and RNA recognition motif-2. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2016]

ARID4B (HGNC:15550): (AT-rich interaction domain 4B) This gene encodes a protein with sequence similarity to retinoblastoma-binding protein-1. The encoded protein is a subunit of the histone deacetylase-dependant SIN3A transcriptional corepressor complex, which functions in diverse cellular processes including proliferation, differentiation, apoptosis, oncogenesis, and cell fate determination. The gene product is recognized by IgG antibody isolated from a breast cancer patient and appears to be a molecular marker associated with a broad range of human malignancies. Alternate transcriptional splice variants encoding different isoforms have been characterized. [provided by RefSeq, Jul 2008]

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
RBM34	NM_015014.4	c.1082G>T	p.Arg361Leu	missense_variant	11/11	ENST00000408888.8	NP_055829.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM34	ENST00000408888.8	c.1082G>T	p.Arg361Leu	missense_variant	11/11	1	NM_015014.4	ENSP00000386226	P1
RBM34	ENST00000447801.5	c.1016G>T	p.Arg339Leu	missense_variant	10/10	5		ENSP00000400000
RBM34	ENST00000495224.1	n.274G>T		non_coding_transcript_exon_variant	3/3	2
ARID4B	ENST00000474953.5	c.*1084G>T		3_prime_UTR_variant, NMD_transcript_variant	17/17	2		ENSP00000420620

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000205 AC: 30 AN: 1460740 Hom.: 0 Cov.: 30 AF XY: 0.0000165 AC XY: 12 AN XY: 726726

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000766

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000497

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

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

Dec 02, 2022

The c.1082G>T (p.R361L) alteration is located in exon 11 (coding exon 11) of the RBM34 gene. This alteration results from a G to T substitution at nucleotide position 1082, causing the arginine (R) at amino acid position 361 to be replaced by a leucine (L). 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	0.50
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T;T
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.82	T;T
M_CAP	Uncertain	0.087	D
MetaRNN	Uncertain	0.45	T;T
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	1.4	L;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.48	T
PROVEAN	Uncertain	-4.4	D;D
REVEL	Uncertain	0.50
Sift	Uncertain	0.0040	D;D
Sift4G	Uncertain	0.0050	D;D
Polyphen		0.93	P;.
Vest4		0.54
MutPred		0.49		Loss of disorder (P = 0.0507);.;
MVP		0.87
MPC		0.42
ClinPred		0.99	D
GERP RS		4.7
Varity_R		0.41
gMVP		0.70

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: rs761837567; hg19: chr1-235295239;