Variant 6-107069207-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001367314.1(BEND3):c.1984G>A(p.Val662Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000453 in 1,612,352 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000048 ( 0 hom. )

Consequence

BEND3
NM_001367314.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.47

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06211108).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BEND3	NM_001367314.1 linkuse as main transcript	c.1984G>A	p.Val662Met	missense_variant	4/4	ENST00000369042.6	NP_001354243.1
BEND3	NM_001080450.3 linkuse as main transcript	c.1984G>A	p.Val662Met	missense_variant	5/5		NP_001073919.1	Q5T5X7
BEND3	XM_005267080.5 linkuse as main transcript	c.1984G>A	p.Val662Met	missense_variant	4/4		XP_005267137.1	Q5T5X7
BEND3	XM_011536005.4 linkuse as main transcript	c.1984G>A	p.Val662Met	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.1984G>A	p.Val662Met	missense_variant	4/4	5	NM_001367314.1	ENSP00000358038.1		Q5T5X7
BEND3	ENST00000429433.3 linkuse as main transcript	c.1984G>A	p.Val662Met	missense_variant	5/5	1		ENSP00000411268.2		Q5T5X7

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000121

AC:

AN:

248138

Hom.:

AF XY:

0.0000223

AC XY:

AN XY:

134746

show subpopulations

Gnomad AFR exome

AF:

0.000129

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000896

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000479

AC:

AN:

1460122

Hom.:

Cov.:

AF XY:

0.0000496

AC XY:

AN XY:

726346

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.00

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:

0.0000558

Gnomad4 OTH exome

AF:

0.0000829

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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 12, 2024

The c.1984G>A (p.V662M) 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 1984, causing the valine (V) at amino acid position 662 to be replaced by a methionine (M). 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

0.096

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.041

T;T

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.062

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.79

.;T

M_CAP

Benign

0.0040

MetaRNN

Benign

0.062

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

N;N

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.38

N;N

REVEL

Benign

0.032

Sift

Benign

0.20

T;T

Sift4G

Benign

0.12

T;T

Polyphen

0.14

B;B

Vest4

0.089

MutPred

0.18

Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);

MVP

0.40

MPC

0.50

ClinPred

0.11

GERP RS

4.3

Varity_R

0.051

gMVP

0.20

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