3-28664273-A-T

Variant names:

• chr3-28664273-A-T
• rs7617877
• ENST00000635992.1:n.*339+87777A>T

GermlineCancer (beta)

Variant summary

Our verdict is Likely benign.

-2 Likely Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -2 classification points (ACMG Germline Pathogenicity v2019). PM2BP4_Strong

The NR_038840.1(LINC00693):n.322+87777A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. Note: NR_038840.1 is not a MANE Select or MANE Plus Clinical transcript for LINC00693; the reported annotation may differ from that of the MANE-designated reference transcript for this gene. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LINC00693 NR_038840.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.285
• Publications: 24 publications found

Genes affected

ENSG00000283563 (HGNC:):

RBMS3 (HGNC:13427): (RNA binding motif single stranded interacting protein 3) This gene encodes an RNA-binding protein that belongs to the c-myc gene single-strand binding protein family. These proteins are characterized by the presence of two sets of ribonucleoprotein consensus sequence (RNP-CS) that contain conserved motifs, RNP1 and RNP2, originally described in RNA binding proteins, and required for DNA binding. These proteins have been implicated in such diverse functions as DNA replication, gene transcription, cell cycle progression and apoptosis. The encoded protein was isolated by virtue of its binding to an upstream element of the alpha2(I) collagen promoter. The observation that this protein localizes mostly in the cytoplasm suggests that it may be involved in a cytoplasmic function such as controlling RNA metabolism, rather than transcription. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2010]

LINC00693 (HGNC:44526): ()

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Likely_benign. The variant received -2 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	PM2Absent/extremely low in population databases		Absent from gnomAD (AR/unknown gene) — PM2; Absent from gnomAD at well-covered site (MOI: unknown) (threshold 0.001) — PM2 moderate.
	BP4Computational evidence suggests no impact		Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); No splicing predictor data available.; Germline computational verdict: benign (Strong).

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NR_038840.1. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	LINC00693 NR_038840.1		n.322+87777A>T	intron	Intron 2 of 4	Prot:

LINC00693 NR_038840.1

HGVSc / HGVSpn.322+87777A>T

Exon rankIntron 2 of 4

intron

Prot:

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	ENSG00000283563 ENST00000635992.1	TSL:5	n.*339+87777A>T	intron	Intron 6 of 13	Prot: ENSP00000489994.1 UniProt:
	RBMS3 ENST00000636680.2	TSL:5	c.213+87777A>T	intron	Intron 1 of 16	Prot: ENSP00000490271.2 UniProt:
	RBMS3 ENST00000432518.6	TSL:5	n.809+87777A>T	intron	Intron 2 of 4	Prot:

ENSG00000283563 ENST00000635992.1

TSL:5

HGVSc / HGVSpn.*339+87777A>T

Exon rankIntron 6 of 13

intron

Prot: ENSP00000489994.1UniProt: A0A1B0GU75

RBMS3 ENST00000636680.2

TSL:5

HGVSc / HGVSpc.213+87777A>T

Exon rankIntron 1 of 16

intron

Prot: ENSP00000490271.2UniProt: A0A1B0GUW5

RBMS3 ENST00000432518.6

TSL:5

HGVSc / HGVSpn.809+87777A>T

Exon rankIntron 2 of 4

intron

Prot:

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 4 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:32
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:32
TOPMed (Bravo)	AF: 0.0000945	AC:	Hom:	AN:	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.00	AC:0	Hom:121691	AN:581790	Cov:

Showing 4 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	5.2
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.20
DANN	Benign	0.68
GPN-Star LLR	N/A	0.29
GPN-Star score	N/A	-0.29
PhyloP100	Benign	-0.28

Showing 7 of 7 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0

Showing 1 of 1 scores

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs7617877;

hg19: chr3-28705764;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar