6-107070136-C-A

Position:

• chr6-107070136-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001367314.1(BEND3):​c.1055G>T​(p.Gly352Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign 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: 3.71

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10283896).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BEND3	NM_001367314.1	c.1055G>T	p.Gly352Val	missense_variant	4/4	ENST00000369042.6	NP_001354243.1
BEND3	NM_001080450.3	c.1055G>T	p.Gly352Val	missense_variant	5/5		NP_001073919.1
BEND3	XM_005267080.5	c.1055G>T	p.Gly352Val	missense_variant	4/4		XP_005267137.1
BEND3	XM_011536005.4	c.1055G>T	p.Gly352Val	missense_variant	5/5		XP_011534307.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BEND3	ENST00000369042.6	c.1055G>T	p.Gly352Val	missense_variant	4/4	5	NM_001367314.1	ENSP00000358038.1
BEND3	ENST00000429433.3	c.1055G>T	p.Gly352Val	missense_variant	5/5	1		ENSP00000411268.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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

Feb 06, 2024

The c.1055G>T (p.G352V) alteration is located in exon 5 (coding exon 3) of the BEND3 gene. This alteration results from a G to T substitution at nucleotide position 1055, causing the glycine (G) at amino acid position 352 to be replaced by a valine (V). 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	0.087
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	16
DANN	Benign	0.84
DEOGEN2	Benign	0.023	T;T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.70	.;T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N;N
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.29	N;N
REVEL	Benign	0.033
Sift	Benign	0.37	T;T
Sift4G	Benign	0.34	T;T
Polyphen		0.0	B;B
Vest4		0.065
MutPred		0.19		Gain of sheet (P = 0.0101);Gain of sheet (P = 0.0101);
MVP		0.27
MPC		0.62
ClinPred		0.33	T
GERP RS		4.2
Varity_R		0.046
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-107391340;