Variant 12-100622288-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_174942.3(GAS2L3):c.662C>G(p.Ala221Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000279 in 1,435,710 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

GAS2L3
NM_174942.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.55

Variant links:

Genes affected

GAS2L3 (HGNC:27475): (growth arrest specific 2 like 3) Enables actin binding activity and microtubule binding activity. Involved in actin cytoskeleton organization and microtubule cytoskeleton organization. Located in actin cytoskeleton and microtubule cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

GAS2L3 links:

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ACMG classification

Classification made for transcript

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
GAS2L3	NM_174942.3 linkuse as main transcript	c.662C>G	p.Ala221Gly	missense_variant	9/10	ENST00000547754.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
GAS2L3	ENST00000547754.6 linkuse as main transcript	c.662C>G	p.Ala221Gly	missense_variant	9/10	1	NM_174942.3	P1
GAS2L3	ENST00000266754.9 linkuse as main transcript	c.662C>G	p.Ala221Gly	missense_variant	8/9	1		P1
GAS2L3	ENST00000539410.2 linkuse as main transcript	c.662C>G	p.Ala221Gly	missense_variant	7/8	2		P1
GAS2L3	ENST00000537247.5 linkuse as main transcript	c.350C>G	p.Ala117Gly	missense_variant	9/10	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248592

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134316

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000887

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000279

AC:

AN:

1435710

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

715666

show subpopulations

Gnomad4 AFR exome

AF:

0.0000305

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:

0.00000275

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Dec 16, 2021

The c.662C>G (p.A221G) alteration is located in exon 9 (coding exon 7) of the GAS2L3 gene. This alteration results from a C to G substitution at nucleotide position 662, causing the alanine (A) at amino acid position 221 to be replaced by a glycine (G). 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

0.66

BayesDel_addAF

Benign

-0.052

BayesDel_noAF

Benign

-0.31

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.054

T;T;T;T

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Pathogenic

0.99

M_CAP

Benign

0.0080

MetaRNN

Uncertain

0.46

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

L;L;.;L

MutationTaster

Benign

0.99

D;D;D;D

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-3.0

D;D;D;D

REVEL

Benign

0.27

Sift

Uncertain

0.0060

D;D;D;D

Sift4G

Benign

0.071

T;T;D;T

Polyphen

0.97

D;D;.;D

Vest4

0.46

MutPred

0.41

Gain of catalytic residue at P225 (P = 2e-04);Gain of catalytic residue at P225 (P = 2e-04);.;Gain of catalytic residue at P225 (P = 2e-04);

MVP

0.52

MPC

0.42

ClinPred

0.86

GERP RS

5.9

Varity_R

0.28

gMVP

0.42

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