Variant 6-107070163-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001367314.1(BEND3):c.1028G>A(p.Arg343Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,460,650 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

BEND3
NM_001367314.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.59

Variant links:

Genes affected

BEND3 (HGNC:23040): (BEN domain containing 3) Enables rDNA binding activity. Involved in several processes, including histone modification; negative regulation of macromolecule metabolic process; and protein homooligomerization. Located in heterochromatin; nucleolus; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

BEND3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.36374047).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BEND3	NM_001367314.1 linkuse as main transcript	c.1028G>A	p.Arg343Gln	missense_variant	4/4	ENST00000369042.6	NP_001354243.1
BEND3	NM_001080450.3 linkuse as main transcript	c.1028G>A	p.Arg343Gln	missense_variant	5/5		NP_001073919.1	Q5T5X7
BEND3	XM_005267080.5 linkuse as main transcript	c.1028G>A	p.Arg343Gln	missense_variant	4/4		XP_005267137.1	Q5T5X7
BEND3	XM_011536005.4 linkuse as main transcript	c.1028G>A	p.Arg343Gln	missense_variant	5/5		XP_011534307.1	Q5T5X7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BEND3	ENST00000369042.6 linkuse as main transcript	c.1028G>A	p.Arg343Gln	missense_variant	4/4	5	NM_001367314.1	ENSP00000358038.1		Q5T5X7
BEND3	ENST00000429433.3 linkuse as main transcript	c.1028G>A	p.Arg343Gln	missense_variant	5/5	1		ENSP00000411268.2		Q5T5X7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1460650

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726634

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 26, 2024

The c.1028G>A (p.R343Q) alteration is located in exon 5 (coding exon 3) of the BEND3 gene. This alteration results from a G to A substitution at nucleotide position 1028, causing the arginine (R) at amino acid position 343 to be replaced by a glutamine (Q). 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

Benign

0.17

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.060

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.091

T;T

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.96

.;D

M_CAP

Benign

0.0047

MetaRNN

Benign

0.36

T;T

MetaSVM

Benign

-0.48

MutationAssessor

Benign

0.97

L;L

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.20

Sift

Uncertain

0.017

D;D

Sift4G

Uncertain

0.032

D;D

Polyphen

1.0

D;D

Vest4

0.30

MutPred

0.64

Gain of disorder (P = 0.1497);Gain of disorder (P = 0.1497);

MVP

0.38

MPC

1.5

ClinPred

0.85

GERP RS

5.1

Varity_R

0.54

gMVP

0.38

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over