Variant 3-100792738-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001375547.2(ABI3BP):c.3977T>C(p.Phe1326Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,902 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

ABI3BP
NM_001375547.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.04

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:

LOC124906260 (HGNC:):

LOC124906260 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28479436).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABI3BP	NM_001375547.2 linkuse as main transcript	c.3977T>C	p.Phe1326Ser	missense_variant	55/68	ENST00000471714.6	NP_001362476.1
LOC124906260	XR_007095986.1 linkuse as main transcript	n.5317A>G		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABI3BP	ENST00000471714.6 linkuse as main transcript	c.3977T>C	p.Phe1326Ser	missense_variant	55/68	5	NM_001375547.2	ENSP00000420524	A2

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151902

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000658

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151902

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74184

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000658

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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

Jun 24, 2022

The c.1919T>C (p.F640S) alteration is located in exon 23 (coding exon 23) of the ABI3BP gene. This alteration results from a T to C substitution at nucleotide position 1919, causing the phenylalanine (F) at amino acid position 640 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

Benign

0.12

BayesDel_addAF

Benign

-0.055

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.018

T;T

Eigen

Benign

0.079

Eigen_PC

Benign

0.11

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.78

T;T

M_CAP

Benign

0.031

MetaRNN

Benign

0.28

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.4

.;M

MutationTaster

Benign

0.99

N;N;N

PrimateAI

Benign

0.46

PROVEAN

Benign

-2.3

N;N

REVEL

Benign

0.16

Sift

Benign

0.084

T;T

Sift4G

Benign

0.46

T;T

Polyphen

0.92

P;P

Vest4

0.52

MutPred

0.12

Loss of glycosylation at K1320 (P = 0.0399);.;

MVP

0.84

MPC

0.39

ClinPred

0.86

GERP RS

4.8

Varity_R

0.13

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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