dbSNP rs1277800826: GLYATL2:p.Pro135Thr (chr11-58837088-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_145016.4(GLYATL2):c.403C>A(p.Pro135Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,376 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict 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. P135L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

GLYATL2
NM_145016.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -4.52

Publications

1 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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05989784).

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.403C>A	p.Pro135Thr	missense	Exon 5 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.403C>A	p.Pro135Thr	missense	Exon 5 of 6	ENSP00000287275.1	Q8WU03
GLYATL2	ENST00000532258.1	TSL:1	c.403C>A	p.Pro135Thr	missense	Exon 6 of 7	ENSP00000434277.1	Q8WU03
GLYATL2	ENST00000533636.1	TSL:3	n.385C>A		non_coding_transcript_exon	Exon 4 of 5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000802

AC:

AN:

249268

AF XY:

0.00000739

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:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461376

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727012

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33464

American (AMR)

AF:

0.00

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39674

South Asian (SAS)

AF:

0.00

AC:

AN:

86242

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000720

AC:

AN:

1111584

Other (OTH)

AF:

0.0000166

AC:

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

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

0.092

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.0020

(source)

DANN

Benign

0.045

DEOGEN2

Benign

0.0013

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.00012

LIST_S2

Benign

0.20

M_CAP

Benign

0.00054

MetaRNN

Benign

0.060

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.40

PhyloP100

-4.5

PrimateAI

Benign

0.32

PROVEAN

Benign

1.1

REVEL

Benign

0.019

Sift

Benign

0.35

Sift4G

Benign

1.0

Polyphen

0.0010

Vest4

0.035

MutPred

0.34

Loss of sheet (P = 0.0043)

MVP

0.099

MPC

0.018

ClinPred

0.13

GERP RS

-3.3

Varity_R

0.033

gMVP

0.11

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over