10-114447934-T-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002313.7(ABLIM1):c.1681A>T(p.Thr561Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ABLIM1 NM_002313.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.18

Genes affected

ABLIM1 (HGNC:78): (actin binding LIM protein 1) This gene encodes a LIM zinc-binding domain-containing protein that binds to actin filaments and mediates interactions between actin and cytoplasmic targets. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jun 2017]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05331701).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABLIM1	NM_002313.7	c.1681A>T	p.Thr561Ser	missense_variant	15/23	ENST00000533213.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABLIM1	ENST00000533213.7	c.1681A>T	p.Thr561Ser	missense_variant	15/23	5	NM_002313.7	A2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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

Feb 12, 2024

The c.1681A>T (p.T561S) alteration is located in exon 15 (coding exon 15) of the ABLIM1 gene. This alteration results from a A to T substitution at nucleotide position 1681, causing the threonine (T) at amino acid position 561 to be replaced by a serine (S). 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	0.13
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
Cadd	Benign	21
Dann	Benign	0.97
Eigen	Benign	-0.18
Eigen_PC	Benign	0.032
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.72	T;T;T;T;T;T;T;T;T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.053	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N;N;N;N;N;N;N;N;N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	0.030	N;.;N;.;.;.;.;.;.
REVEL	Benign	0.033
Sift	Benign	0.43	T;.;T;.;.;.;.;.;.
Sift4G	Benign	0.55	T;T;T;T;T;T;T;T;.
Polyphen		0.0040	B;.;B;.;B;.;.;B;.
Vest4		0.19
MutPred		0.22		.;.;.;.;.;.;.;Gain of helix (P = 0.062);.;
MVP		0.18
MPC		0.33
ClinPred		0.61	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.047
gMVP		0.32

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: chr10-116207693;