10-114447994-A-C

Position:

• chr10-114447994-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002313.7(ABLIM1):​c.1621T>G​(p.Ser541Ala) 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. 12/21 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: 2.45

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14984259).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABLIM1	NM_002313.7	c.1621T>G	p.Ser541Ala	missense_variant	15/23	ENST00000533213.7	NP_002304.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABLIM1	ENST00000533213.7	c.1621T>G	p.Ser541Ala	missense_variant	15/23	5	NM_002313.7	ENSP00000433629	A2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

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

Sep 20, 2023

The c.1621T>G (p.S541A) alteration is located in exon 15 (coding exon 15) of the ABLIM1 gene. This alteration results from a T to G substitution at nucleotide position 1621, causing the serine (S) at amino acid position 541 to be replaced by an alanine (A). 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	0.085
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.027	.;.;.;T;.;T;.;T;.
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.059
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.65	T;T;T;T;T;T;T;T;T
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.15	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.51	.;.;.;.;.;.;.;N;.
MutationTaster	Benign	0.84	D;D;D;D;N;N;N;N;N
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.5	N;.;N;.;D;N;N;.;.
REVEL	Benign	0.023
Sift	Benign	0.048	D;.;D;.;D;D;T;.;.
Sift4G	Benign	0.41	T;T;T;T;T;T;T;T;.
Polyphen		0.0010	B;.;B;.;B;.;.;B;.
Vest4		0.27
MutPred		0.29		.;.;.;.;.;.;.;Loss of phosphorylation at S541 (P = 0.0464);.;
MVP		0.69
MPC		0.32
ClinPred		0.78	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.41

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: chr10-116207753;