Variant 5-149233250-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2

The NM_014945.5(ABLIM3):c.838T>C(p.Ser280Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000434 in 1,614,058 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ABLIM3
NM_014945.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.18

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 4 ACMG points.

PM1

In a modified_residue Phosphoserine (size 0) in uniprot entity ABLM3_HUMAN

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABLIM3	NM_014945.5 linkuse as main transcript	c.838T>C	p.Ser280Pro	missense_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.838T>C	p.Ser280Pro	missense_variant	10/24	1	NM_014945.5	ENSP00000310309.7		O94929-1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461876

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727240

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:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Bravo

AF:

0.000117

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

Nov 08, 2024

The c.838T>C (p.S280P) alteration is located in exon 10 (coding exon 9) of the ABLIM3 gene. This alteration results from a T to C substitution at nucleotide position 838, causing the serine (S) at amino acid position 280 to be replaced by a proline (P). 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

Pathogenic

0.29

BayesDel_noAF

Pathogenic

0.18

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

.;T;T;.;.

Eigen

Uncertain

0.65

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.90

D;.;D;D;D

M_CAP

Benign

0.039

MetaRNN

Uncertain

0.67

D;D;D;D;D

MetaSVM

Benign

-0.41

MutationAssessor

Uncertain

2.2

M;M;M;M;.

PrimateAI

Pathogenic

0.82

PROVEAN

Uncertain

-2.6

D;D;D;D;D

REVEL

Benign

0.29

Sift

Uncertain

0.020

D;D;D;D;D

Sift4G

Benign

0.17

T;T;T;T;T

Polyphen

0.99

D;P;P;D;.

Vest4

0.81

MutPred

0.19

Loss of phosphorylation at S280 (P = 0.01);Loss of phosphorylation at S280 (P = 0.01);Loss of phosphorylation at S280 (P = 0.01);Loss of phosphorylation at S280 (P = 0.01);Loss of phosphorylation at S280 (P = 0.01);

MVP

0.81

MPC

0.67

ClinPred

0.93

GERP RS

6.0

Varity_R

0.63

gMVP

0.62

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.

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