Genetic Variant GLYATL2:p.Met42Arg (chr11-58838322-A-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_145016.4(GLYATL2):c.125T>G(p.Met42Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000992 in 1,613,454 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M42L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 3 hom. )

Consequence

GLYATL2
NM_145016.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.30

Publications

2 publications found

Variant links:

Genes affected

GLYATL2 (HGNC:24178): (glycine-N-acyltransferase like 2) Enables glycine N-acyltransferase activity. Involved in long-chain fatty acid catabolic process; medium-chain fatty acid catabolic process; and monounsaturated fatty acid catabolic process. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

GLYATL2 links:

ENSG00000289621 (HGNC:):

ENSG00000289621 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145016.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLYATL2	NM_145016.4	MANE Select	c.125T>G	p.Met42Arg	missense	Exon 3 of 6	NP_659453.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GLYATL2	ENST00000287275.6	TSL:1 MANE Select	c.125T>G	p.Met42Arg	missense	Exon 3 of 6	ENSP00000287275.1	Q8WU03
GLYATL2	ENST00000532258.1	TSL:1	c.125T>G	p.Met42Arg	missense	Exon 4 of 7	ENSP00000434277.1	Q8WU03
GLYATL2	ENST00000533636.1	TSL:3	n.107T>G		non_coding_transcript_exon	Exon 2 of 5

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000136

AC:

AN:

249330

AF XY:

0.000192

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000133

Gnomad OTH exome

AF:

0.000661

GnomAD4 exome

AF:

0.000107

AC:

157

AN:

1461170

Hom.:

Cov.:

AF XY:

0.000150

AC XY:

109

AN XY:

726908

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33442

American (AMR)

AF:

0.00

AC:

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26100

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.000464

AC:

AN:

86238

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0000855

AC:

AN:

1111476

Other (OTH)

AF:

0.000348

AC:

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152284

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41570

American (AMR)

AF:

0.00

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.000207

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000785

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.000149

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.024

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.71

M_CAP

Benign

0.0051

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

PhyloP100

2.3

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-4.2

REVEL

Benign

0.062

Sift

Uncertain

0.012

Sift4G

Pathogenic

0.0010

Polyphen

0.26

Vest4

0.42

MutPred

0.76

Loss of ubiquitination at K37 (P = 0.0468)

MVP

0.055

MPC

0.044

ClinPred

0.10

GERP RS

3.6

Varity_R

0.67

gMVP

0.43

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.23

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.23

Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over