chr5-149239258-C-T

Position:

• chr5-149239258-C-T

Variant summary

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

The NM_014945.5(ABLIM3):​c.1055C>T​(p.Thr352Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ABLIM3 NM_014945.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.94

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]

(HGNC:):

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	UniProt
ABLIM3	NM_014945.5	c.1055C>T	p.Thr352Ile	missense_variant	12/24	ENST00000309868.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABLIM3	ENST00000309868.12	c.1055C>T	p.Thr352Ile	missense_variant	12/24	1	NM_014945.5	P1
	ENST00000522685.1	n.87+37432G>A		intron_variant, non_coding_transcript_variant		2
	ENST00000523176.1	n.117-18319G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Nov 07, 2023

The c.1055C>T (p.T352I) alteration is located in exon 12 (coding exon 11) of the ABLIM3 gene. This alteration results from a C to T substitution at nucleotide position 1055, causing the threonine (T) at amino acid position 352 to be replaced by an isoleucine (I). 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	0.26
BayesDel_addAF	Uncertain	0.099	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T;T;.
Eigen	Benign	0.039
Eigen_PC	Benign	0.21
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.62	D;D;D
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.1	M;M;.
MutationTaster	Benign	1.0	D;D;D;D;D;D
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-2.4	N;N;N
REVEL	Benign	0.20
Sift	Benign	0.038	D;D;D
Sift4G	Benign	0.18	T;T;T
Polyphen		0.059	B;B;.
Vest4		0.75
MutPred		0.30		Loss of glycosylation at T352 (P = 0.0846);Loss of glycosylation at T352 (P = 0.0846);Loss of glycosylation at T352 (P = 0.0846);
MVP		0.65
MPC		0.15
ClinPred		0.98	D
GERP RS		5.1
Varity_R		0.18
gMVP		0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr5-148618821;