3-100780206-A-T

Position:

• chr3-100780206-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001375547.2(ABI3BP):​c.4166T>A​(p.Val1389Asp) 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 benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ABI3BP NM_001375547.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.501

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09123209).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABI3BP	NM_001375547.2	c.4166T>A	p.Val1389Asp	missense_variant	58/68	ENST00000471714.6	NP_001362476.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABI3BP	ENST00000471714.6	c.4166T>A	p.Val1389Asp	missense_variant	58/68	5	NM_001375547.2	ENSP00000420524	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Jan 26, 2022

The c.2033T>A (p.V678D) alteration is located in exon 25 (coding exon 25) of the ABI3BP gene. This alteration results from a T to A substitution at nucleotide position 2033, causing the valine (V) at amino acid position 678 to be replaced by an aspartic acid (D). 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	0.15
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	18
DANN	Benign	0.87
DEOGEN2	Benign	0.025	T;T;T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.054	N
LIST_S2	Benign	0.82	T;T;.
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.091	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	.;L;.
MutationTaster	Benign	0.97	N;N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.5	N;N;N
REVEL	Benign	0.15
Sift	Benign	0.13	T;D;T
Sift4G	Benign	0.68	T;T;.
Polyphen		0.99	D;B;.
Vest4		0.39
MutPred		0.19		Gain of glycosylation at T1378 (P = 0.0065);.;.;
MVP		0.60
MPC		0.19
ClinPred		0.12	T
GERP RS		0.77
Varity_R		0.10
gMVP		0.34

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: chr3-100499050;