3-100753840-T-C

Position:

• chr3-100753840-T-C

Variant summary

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

The NM_001375547.2(ABI3BP):​c.4939A>G​(p.Arg1647Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,458,284 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: 0.0000027 (0 hom.)
• Consequence: ABI3BP NM_001375547.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.88

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 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
ABI3BP	NM_001375547.2	c.4939A>G	p.Arg1647Gly	missense_variant	65/68	ENST00000471714.6	NP_001362476.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABI3BP	ENST00000471714.6	c.4939A>G	p.Arg1647Gly	missense_variant	65/68	5	NM_001375547.2	ENSP00000420524	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1458284 Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 2 AN XY: 724946

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: 0.00000360

Gnomad4 OTH exome AF: 0.00

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

Aug 28, 2023

The c.2806A>G (p.R936G) alteration is located in exon 32 (coding exon 32) of the ABI3BP gene. This alteration results from a A to G substitution at nucleotide position 2806, causing the arginine (R) at amino acid position 936 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	Pathogenic	0.97
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T;T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Benign	0.040	D
MetaRNN	Uncertain	0.58	D;D
MetaSVM	Benign	-0.48	T
MutationAssessor	Benign	2.0	.;M
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-5.4	D;D
REVEL	Uncertain	0.30
Sift	Uncertain	0.0050	D;D
Sift4G	Uncertain	0.010	D;D
Polyphen		0.99	D;D
Vest4		0.61
MutPred		0.23		Gain of catalytic residue at R1638 (P = 0.0116);.;
MVP		0.94
MPC		0.50
ClinPred		0.99	D
GERP RS		3.3
Varity_R		0.63
gMVP		0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: chr3-100472684;