6-107068841-C-T

Position:

• chr6-107068841-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001367314.1(BEND3):​c.2350G>A​(p.Val784Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: BEND3 NM_001367314.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.52

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.849

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BEND3	NM_001367314.1	c.2350G>A	p.Val784Met	missense_variant	4/4	ENST00000369042.6	NP_001354243.1
BEND3	NM_001080450.3	c.2350G>A	p.Val784Met	missense_variant	5/5		NP_001073919.1
BEND3	XM_005267080.5	c.2350G>A	p.Val784Met	missense_variant	4/4		XP_005267137.1
BEND3	XM_011536005.4	c.2350G>A	p.Val784Met	missense_variant	5/5		XP_011534307.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BEND3	ENST00000369042.6	c.2350G>A	p.Val784Met	missense_variant	4/4	5	NM_001367314.1	ENSP00000358038.1
BEND3	ENST00000429433.3	c.2350G>A	p.Val784Met	missense_variant	5/5	1		ENSP00000411268.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000658 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 11, 2024

The c.2350G>A (p.V784M) 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 2350, causing the valine (V) at amino acid position 784 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	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T;T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	.;D
M_CAP	Benign	0.046	D
MetaRNN	Pathogenic	0.85	D;D
MetaSVM	Benign	-0.49	T
MutationAssessor	Benign	1.8	L;L
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-1.9	N;N
REVEL	Uncertain	0.42
Sift	Uncertain	0.0020	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.88
MVP		0.74
MPC		1.4
ClinPred		0.93	D
GERP RS		4.5
Varity_R		0.29
gMVP		0.71

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

Other links and lift over

dbSNP: rs782795224; hg19: chr6-107390045;