Variant 3-100778370-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001375547.2(ABI3BP):c.4247G>A(p.Arg1416His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000359 in 1,585,636 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000076 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

ABI3BP
NM_001375547.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.124

Variant links:

Genes affected

ABI3BP (HGNC:17265): (ABI family member 3 binding protein) Predicted to enable actin filament binding activity and glycosaminoglycan binding activity. Predicted to be involved in regulation of actin cytoskeleton reorganization; regulation of dendritic spine morphogenesis; and regulation of postsynaptic density assembly. Predicted to act upstream of or within extracellular matrix organization and positive regulation of cell-substrate adhesion. Located in extracellular space. Colocalizes with collagen-containing extracellular matrix. [provided by Alliance of Genome Resources, Apr 2022]

ABI3BP links:

ABI3BP (HGNC:):

ABI3BP links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.040719897).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABI3BP	NM_001375547.2 linkuse as main transcript	c.4247G>A	p.Arg1416His	missense_variant	59/68	ENST00000471714.6	NP_001362476.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABI3BP	ENST00000471714.6 linkuse as main transcript	c.4247G>A	p.Arg1416His	missense_variant	59/68	5	NM_001375547.2	ENSP00000420524.2		D3YTG3

Frequencies

GnomAD3 genomes

AF:

0.0000760

AC:

AN:

131518

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000143

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000247

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000672

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000569

AC:

AN:

246046

Hom.:

AF XY:

0.0000599

AC XY:

AN XY:

133544

show subpopulations

Gnomad AFR exome

AF:

0.0000652

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000998

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000715

Gnomad OTH exome

AF:

0.000337

GnomAD4 exome

AF:

0.0000323

AC:

AN:

1453994

Hom.:

Cov.:

AF XY:

0.0000401

AC XY:

AN XY:

723110

show subpopulations

Gnomad4 AFR exome

AF:

0.0000301

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000235

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000361

Gnomad4 OTH exome

AF:

0.0000666

GnomAD4 genome

AF:

0.0000760

AC:

AN:

131642

Hom.:

Cov.:

AF XY:

0.0000620

AC XY:

AN XY:

64538

show subpopulations

Gnomad4 AFR

AF:

0.000142

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000248

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000672

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000475

Hom.:

Bravo

AF:

0.0000453

ExAC

AF:

0.0000579

AC:

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

Dec 09, 2024

The c.2114G>A (p.R705H) alteration is located in exon 26 (coding exon 26) of the ABI3BP gene. This alteration results from a G to A substitution at nucleotide position 2114, causing the arginine (R) at amino acid position 705 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

Benign

0.086

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.021

T;T;T

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.036

LIST_S2

Uncertain

0.87

D;D;.

M_CAP

Benign

0.0086

MetaRNN

Benign

0.041

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

.;L;.

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.6

N;N;N

REVEL

Benign

0.023

Sift

Benign

0.13

T;T;D

Sift4G

Benign

0.21

T;T;.

Polyphen

0.50

P;B;.

Vest4

0.26

MutPred

0.26

Loss of glycosylation at P1412 (P = 0.0071);.;.;

MVP

0.34

MPC

0.54

ClinPred

0.072

GERP RS

1.3

Varity_R

0.017

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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