Variant 5-149233299-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_014945.5(ABLIM3):c.887G>A(p.Cys296Tyr) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,461,750 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

ABLIM3
NM_014945.5 missense, splice_region

Scores

Splicing: ADA: 0.005927

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.98

Variant links:

Genes affected

ABLIM3 (HGNC:29132): (actin binding LIM protein family member 3) This gene encodes a member of the actin-binding LIM (abLIM) family of proteins. These proteins are characterized by an N-terminal LIM domain and a C-terminal dematin-like domain. The encoded protein interacts with actin filaments and may be a component of adherens junctions in several cell types. A variant of this gene may be associated with pain sensitivity in male human patients. [provided by RefSeq, Sep 2016]

ABLIM3 links:

ENSG00000253406 (HGNC:):

ENSG00000253406 links:

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ACMG classification

Classification made for transcript

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, 0.834

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABLIM3	NM_014945.5 linkuse as main transcript	c.887G>A	p.Cys296Tyr	missense_variant, splice_region_variant	10/24	ENST00000309868.12	NP_055760.1	O94929-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABLIM3	ENST00000309868.12 linkuse as main transcript	c.887G>A	p.Cys296Tyr	missense_variant, splice_region_variant	10/24	1	NM_014945.5	ENSP00000310309.7		O94929-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251472

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1461750

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

727196

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000899

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

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 21, 2023

The c.887G>A (p.C296Y) alteration is located in exon 10 (coding exon 9) of the ABLIM3 gene. This alteration results from a G to A substitution at nucleotide position 887, causing the cysteine (C) at amino acid position 296 to be replaced by a tyrosine (Y). 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

0.63

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

0.080

CADD

Pathogenic

DANN

Benign

0.89

DEOGEN2

Benign

0.037

.;T;T;.;.

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.77

T;.;D;T;D

M_CAP

Benign

0.043

MetaRNN

Pathogenic

0.83

D;D;D;D;D

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.2

L;L;L;L;.

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

2.7

N;N;N;N;N

REVEL

Uncertain

0.43

Sift

Benign

1.0

T;T;T;T;T

Sift4G

Benign

1.0

T;T;T;T;T

Polyphen

1.0

D;D;D;D;.

Vest4

0.94

MutPred

0.76

Gain of phosphorylation at C296 (P = 0.0391);Gain of phosphorylation at C296 (P = 0.0391);Gain of phosphorylation at C296 (P = 0.0391);Gain of phosphorylation at C296 (P = 0.0391);Gain of phosphorylation at C296 (P = 0.0391);

MVP

0.63

MPC

0.76

ClinPred

0.59

GERP RS

6.0

Varity_R

0.15

gMVP

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0059

dbscSNV1_RF

Benign

0.084

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.

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