3-100752829-T-G

Variant names:

• chr3-100752829-T-G
• NM_001375547.2:c.5080A>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001375547.2(ABI3BP):​c.5080A>C​(p.Asn1694His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: 7.88

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.758

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABI3BP	NM_001375547.2	c.5080A>C	p.Asn1694His	missense_variant	Exon 66 of 68	ENST00000471714.6	NP_001362476.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABI3BP	ENST00000471714.6	c.5080A>C	p.Asn1694His	missense_variant	Exon 66 of 68	5	NM_001375547.2	ENSP00000420524.2

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

Dec 18, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2947A>C (p.N983H) alteration is located in exon 33 (coding exon 33) of the ABI3BP gene. This alteration results from a A to C substitution at nucleotide position 2947, causing the asparagine (N) at amino acid position 983 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	Pathogenic	0.84
BayesDel_addAF	Uncertain	0.078	D
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.40	T;T
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.84
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	1.0	D;D
M_CAP	Uncertain	0.093	D
MetaRNN	Pathogenic	0.76	D;D
MetaSVM	Uncertain	-0.19	T
MutationAssessor	Uncertain	2.3	.;M
PrimateAI	Pathogenic	0.81	D
PROVEAN	Pathogenic	-4.6	D;D
REVEL	Uncertain	0.41
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.99	D;D
Vest4		0.72
MutPred		0.30		Loss of MoRF binding (P = 0.1053);.;
MVP		0.91
MPC		0.50
ClinPred		0.99	D
GERP RS		6.0
Varity_R		0.69
gMVP		0.61

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: chr3-100471673;