Variant 6-107069312-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3

The NM_001367314.1(BEND3):c.1879A>C(p.Asn627His) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0027 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

BEND3
NM_001367314.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.63

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 Uncertain_significance. Variant got 1 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.787

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BEND3	NM_001367314.1 linkuse as main transcript	c.1879A>C	p.Asn627His	missense_variant	4/4	ENST00000369042.6	NP_001354243.1
BEND3	NM_001080450.3 linkuse as main transcript	c.1879A>C	p.Asn627His	missense_variant	5/5		NP_001073919.1	Q5T5X7
BEND3	XM_005267080.5 linkuse as main transcript	c.1879A>C	p.Asn627His	missense_variant	4/4		XP_005267137.1	Q5T5X7
BEND3	XM_011536005.4 linkuse as main transcript	c.1879A>C	p.Asn627His	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.1879A>C	p.Asn627His	missense_variant	4/4	5	NM_001367314.1	ENSP00000358038.1		Q5T5X7
BEND3	ENST00000429433.3 linkuse as main transcript	c.1879A>C	p.Asn627His	missense_variant	5/5	1		ENSP00000411268.2		Q5T5X7

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

148966

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000123

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000469

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00130

Gnomad SAS

AF:

0.00309

Gnomad FIN

AF:

0.0000965

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000593

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00269

AC:

3552

AN:

1319152

Hom.:

Cov.:

AF XY:

0.00246

AC XY:

1617

AN XY:

658162

show subpopulations

Gnomad4 AFR exome

AF:

0.00449

Gnomad4 AMR exome

AF:

0.00220

Gnomad4 ASJ exome

AF:

0.00721

Gnomad4 EAS exome

AF:

0.00818

Gnomad4 SAS exome

AF:

0.000713

Gnomad4 FIN exome

AF:

0.00612

Gnomad4 NFE exome

AF:

0.00227

Gnomad4 OTH exome

AF:

0.00529

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000235

AC:

AN:

149110

Hom.:

Cov.:

AF XY:

0.000206

AC XY:

AN XY:

72856

show subpopulations

Gnomad4 AFR

AF:

0.000122

Gnomad4 AMR

AF:

0.000469

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00131

Gnomad4 SAS

AF:

0.00285

Gnomad4 FIN

AF:

0.0000965

Gnomad4 NFE

AF:

0.0000593

Gnomad4 OTH

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

Jun 07, 2024

The c.1879A>C (p.N627H) alteration is located in exon 5 (coding exon 3) of the BEND3 gene. This alteration results from a A to C substitution at nucleotide position 1879, causing the asparagine (N) at amino acid position 627 to be replaced by a histidine (H). 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

0.54

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Benign

-0.090

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.25

T;T

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.87

.;D

M_CAP

Benign

0.024

MetaRNN

Pathogenic

0.79

D;D

MetaSVM

Benign

-0.65

MutationAssessor

Benign

0.81

L;L

PrimateAI

Uncertain

0.79

PROVEAN

Uncertain

-2.8

D;D

REVEL

Uncertain

0.48

Sift

Uncertain

0.0070

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.63

MutPred

0.77

Loss of solvent accessibility (P = 0.0595);Loss of solvent accessibility (P = 0.0595);

MVP

0.35

MPC

1.4

ClinPred

0.99

GERP RS

4.6

Varity_R

0.42

gMVP

0.59

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