Variant 1-48727938-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_024603.4(BEND5):c.1214A>G(p.Asn405Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,652 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

BEND5
NM_024603.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.63

Variant links:

Genes affected

BEND5 (HGNC:25668): (BEN domain containing 5) Predicted to enable DNA binding activity. Involved in negative regulation of transcription, DNA-templated. Predicted to be located in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

BEND5 links:

AGBL4 (HGNC:25892): (AGBL carboxypeptidase 4) Predicted to enable metallocarboxypeptidase activity and tubulin binding activity. Predicted to be involved in C-terminal protein deglutamylation; defense response to virus; and protein side chain deglutamylation. Predicted to act upstream of or within several processes, including axonal transport of mitochondrion; positive regulation of ubiquitin-dependent protein catabolic process; and regulation of blastocyst development. Located in Golgi apparatus; centriole; and ciliary basal body. [provided by Alliance of Genome Resources, Apr 2022]

AGBL4 links:

BEND5 (HGNC:):

BEND5 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BEND5	NM_024603.4 linkuse as main transcript	c.1214A>G	p.Asn405Ser	missense_variant	6/6	ENST00000371833.4	NP_078879.2	Q7L4P6-1A0A0S2Z5N0
AGBL4	NM_032785.4 linkuse as main transcript	c.635-64697A>G		intron_variant		ENST00000371839.6	NP_116174.3	Q5VU57-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BEND5	ENST00000371833.4 linkuse as main transcript	c.1214A>G	p.Asn405Ser	missense_variant	6/6	1	NM_024603.4	ENSP00000360899.3		Q7L4P6-1
AGBL4	ENST00000371839.6 linkuse as main transcript	c.635-64697A>G		intron_variant		2	NM_032785.4	ENSP00000360905.1		Q5VU57-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1459652

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726068

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Jul 11, 2022

The c.1214A>G (p.N405S) alteration is located in exon 6 (coding exon 6) of the BEND5 gene. This alteration results from a A to G substitution at nucleotide position 1214, causing the asparagine (N) at amino acid position 405 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

Pathogenic

0.96

BayesDel_addAF

Benign

-0.079

BayesDel_noAF

Benign

-0.35

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.010

MetaRNN

Uncertain

0.62

MetaSVM

Benign

-0.70

MutationAssessor

Benign

1.2

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-1.8

REVEL

Benign

0.26

Sift

Benign

0.24

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.70

MutPred

0.11

Loss of helix (P = 0.0558);

MVP

0.54

MPC

1.5

ClinPred

0.92

GERP RS

5.8

Varity_R

0.20

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