3-100792744-T-C

Variant summary

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

The NM_001375547.2(ABI3BP):ā€‹c.3971A>Gā€‹(p.Glu1324Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,611,504 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000041 ( 0 hom. )

Consequence

ABI3BP
NM_001375547.2 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.16
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]

Genome browser will be placed here

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=0.056230724).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ABI3BPNM_001375547.2 linkuse as main transcriptc.3971A>G p.Glu1324Gly missense_variant 55/68 ENST00000471714.6 NP_001362476.1
LOC124906260XR_007095986.1 linkuse as main transcriptn.5323T>C non_coding_transcript_exon_variant 2/2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ABI3BPENST00000471714.6 linkuse as main transcriptc.3971A>G p.Glu1324Gly missense_variant 55/685 NM_001375547.2 ENSP00000420524 A2

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
151920
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000208
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000805
AC:
2
AN:
248482
Hom.:
0
AF XY:
0.00000742
AC XY:
1
AN XY:
134818
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000888
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000411
AC:
6
AN:
1459584
Hom.:
0
Cov.:
30
AF XY:
0.00000551
AC XY:
4
AN XY:
726064
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:
0.0000580
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.01e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
151920
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74210
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000208
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 submitterclinical testingAmbry GeneticsNov 30, 2021The c.1913A>G (p.E638G) alteration is located in exon 23 (coding exon 23) of the ABI3BP gene. This alteration results from a A to G substitution at nucleotide position 1913, causing the glutamic acid (E) at amino acid position 638 to be replaced by a glycine (G). 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
0.094
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
11
DANN
Uncertain
0.99
DEOGEN2
Benign
0.032
T;T
Eigen
Benign
-0.32
Eigen_PC
Benign
-0.33
FATHMM_MKL
Benign
0.17
N
LIST_S2
Benign
0.68
T;T
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.056
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.7
.;L
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.31
T
PROVEAN
Uncertain
-2.7
D;D
REVEL
Benign
0.092
Sift
Benign
0.13
T;T
Sift4G
Benign
0.21
T;T
Polyphen
0.017
B;B
Vest4
0.28
MutPred
0.14
Loss of glycosylation at K1320 (P = 0.0399);.;
MVP
0.84
MPC
0.26
ClinPred
0.13
T
GERP RS
4.5
Varity_R
0.095
gMVP
0.29

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.

Other links and lift over

dbSNP: rs1373428474; hg19: chr3-100511588; API