Variant 6-107069533-C-G 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.1658G>C(p.Cys553Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000298 in 1,613,002 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: 0.000031 ( 0 hom. )

Consequence

BEND3
NM_001367314.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.45

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 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=0.03787908).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BEND3	NM_001367314.1 linkuse as main transcript	c.1658G>C	p.Cys553Ser	missense_variant	4/4	ENST00000369042.6	NP_001354243.1
BEND3	NM_001080450.3 linkuse as main transcript	c.1658G>C	p.Cys553Ser	missense_variant	5/5		NP_001073919.1	Q5T5X7
BEND3	XM_005267080.5 linkuse as main transcript	c.1658G>C	p.Cys553Ser	missense_variant	4/4		XP_005267137.1	Q5T5X7
BEND3	XM_011536005.4 linkuse as main transcript	c.1658G>C	p.Cys553Ser	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.1658G>C	p.Cys553Ser	missense_variant	4/4	5	NM_001367314.1	ENSP00000358038.1		Q5T5X7
BEND3	ENST00000429433.3 linkuse as main transcript	c.1658G>C	p.Cys553Ser	missense_variant	5/5	1		ENSP00000411268.2		Q5T5X7

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000164

AC:

AN:

249688

Hom.:

AF XY:

0.000162

AC XY:

AN XY:

135392

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00119

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000308

AC:

AN:

1460846

Hom.:

Cov.:

AF XY:

0.0000303

AC XY:

AN XY:

726752

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00101

Gnomad4 ASJ exome

AF:

0.00

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:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152156

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000453

ExAC

AF:

0.000115

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

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

Oct 07, 2024

The c.1658G>C (p.C553S) alteration is located in exon 5 (coding exon 3) of the BEND3 gene. This alteration results from a G to C substitution at nucleotide position 1658, causing the cysteine (C) at amino acid position 553 to be replaced by a serine (S). 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

0.20

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.050

T;T

Eigen

Benign

-0.20

Eigen_PC

Benign

0.024

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.59

.;T

M_CAP

Benign

0.0018

MetaRNN

Benign

0.038

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.010

N;N

REVEL

Benign

0.20

Sift

Benign

0.40

T;T

Sift4G

Uncertain

0.047

D;D

Polyphen

0.0030

B;B

Vest4

0.28

MutPred

0.54

Gain of disorder (P = 6e-04);Gain of disorder (P = 6e-04);

MVP

0.26

MPC

0.63

ClinPred

0.091

GERP RS

4.1

Varity_R

0.047

gMVP

0.52

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