6-107069360-T-A

Position:

• chr6-107069360-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001367314.1(BEND3):​c.1831A>T​(p.Ile611Phe) variant causes a missense change involving the alteration of a non-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: 3.00

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.778

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BEND3	NM_001367314.1	c.1831A>T	p.Ile611Phe	missense_variant	4/4	ENST00000369042.6	NP_001354243.1
BEND3	NM_001080450.3	c.1831A>T	p.Ile611Phe	missense_variant	5/5		NP_001073919.1
BEND3	XM_005267080.5	c.1831A>T	p.Ile611Phe	missense_variant	4/4		XP_005267137.1
BEND3	XM_011536005.4	c.1831A>T	p.Ile611Phe	missense_variant	5/5		XP_011534307.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BEND3	ENST00000369042.6	c.1831A>T	p.Ile611Phe	missense_variant	4/4	5	NM_001367314.1	ENSP00000358038.1
BEND3	ENST00000429433.3	c.1831A>T	p.Ile611Phe	missense_variant	5/5	1		ENSP00000411268.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

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

Nov 18, 2022

The c.1831A>T (p.I611F) alteration is located in exon 5 (coding exon 3) of the BEND3 gene. This alteration results from a A to T substitution at nucleotide position 1831, causing the isoleucine (I) at amino acid position 611 to be replaced by a phenylalanine (F). 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	0.87
BayesDel_addAF	Uncertain	0.038	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.078	T;T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.89	.;D
M_CAP	Benign	0.014	T
MetaRNN	Pathogenic	0.78	D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;N
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.23
Sift	Uncertain	0.0060	D;D
Sift4G	Uncertain	0.013	D;D
Polyphen		0.99	D;D
Vest4		0.68
MutPred		0.61		Loss of stability (P = 0.0676);Loss of stability (P = 0.0676);
MVP		0.58
MPC		1.7
ClinPred		0.86	D
GERP RS		4.9
Varity_R		0.20
gMVP		0.82

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: chr6-107390564;