dbSNP rs201611635: ABLIM2:p.Arg560Pro (chr4-7992867-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001130083.2(ABLIM2):c.1679G>C(p.Arg560Pro) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,140 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R560Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ABLIM2
NM_001130083.2 missense, splice_region

Scores

Splicing: ADA: 0.0003870

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.49

Variant links:

Genes affected

ABLIM2 (HGNC:19195): (actin binding LIM protein family member 2) Predicted to enable actin filament binding activity. Predicted to be involved in lamellipodium assembly. Predicted to act upstream of or within positive regulation of transcription by RNA polymerase II. Located in actin cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

ABLIM2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26689392).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABLIM2	NM_001130083.2 link	c.1679G>C	p.Arg560Pro	missense_variant, splice_region_variant	Exon 17 of 21	ENST00000447017.7	NP_001123555.1	Q6H8Q1-9A0A140VK02

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABLIM2	ENST00000447017.7 link	c.1679G>C	p.Arg560Pro	missense_variant, splice_region_variant	Exon 17 of 21	1	NM_001130083.2	ENSP00000393511.2		Q6H8Q1-9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000812

AC:

AN:

246402

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

133904

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000665

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460140

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726160

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:

0.0000233

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000830

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Benign

0.69

DEOGEN2

Benign

0.020

.;.;T;T;.

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.77

T;T;T;T;T

M_CAP

Benign

0.0059

MetaRNN

Benign

0.27

T;T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.68

.;.;N;.;.

PrimateAI

Benign

0.46

PROVEAN

Benign

0.48

N;N;N;.;N

REVEL

Benign

0.22

Sift

Benign

0.26

T;T;T;.;T

Sift4G

Benign

0.44

T;T;T;T;T

Polyphen

0.29

B;.;B;.;.

Vest4

0.53

MutPred

0.38

.;.;Gain of disorder (P = 0.0847);.;.;

MVP

0.70

MPC

0.067

ClinPred

0.13

GERP RS

3.8

Varity_R

0.18

gMVP

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00039

dbscSNV1_RF

Benign

0.048

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over