Genetic Variant GLYAT:p.Asp174Asn (chr11-58710137-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_201648.3(GLYAT):c.520G>A(p.Asp174Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,466 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. D174H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

GLYAT
NM_201648.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.443

Publications

23 publications found

Variant links:

Genes affected

GLYAT (HGNC:13734): (glycine-N-acyltransferase) The glycine-N-acyltransferase protein conjugates glycine with acyl-CoA substrates in the mitochondria. The protein is thought to be important in the detoxification of endogenous and xenobiotic acyl-CoA's. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

GLYAT links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_201648.3. 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
	GLYAT	NM_201648.3	MANE Select	c.520G>A	p.Asp174Asn	missense	Exon 6 of 6	NP_964011.2	A0A384P5E3
	GLYAT	NM_005838.4		c.*449G>A		3_prime_UTR	Exon 5 of 5	NP_005829.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GLYAT	ENST00000344743.8	TSL:1 MANE Select	c.520G>A	p.Asp174Asn	missense	Exon 6 of 6	ENSP00000340200.3	Q6IB77-1
GLYAT	ENST00000278400.3	TSL:1	c.*449G>A		3_prime_UTR	Exon 5 of 5	ENSP00000278400.3	Q6IB77-2
GLYAT	ENST00000529732.5	TSL:5	c.520G>A	p.Asp174Asn	missense	Exon 6 of 6	ENSP00000431688.1	Q6IB77-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000799

AC:

AN:

250422

AF XY:

0.00000739

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461466

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726998

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33466

American (AMR)

AF:

0.0000224

AC:

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26102

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.00

AC:

AN:

86202

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53380

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111790

Other (OTH)

AF:

0.00

AC:

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.75

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.052

LIST_S2

Benign

0.78

M_CAP

Benign

0.014

MetaRNN

Benign

0.39

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.5

PhyloP100

0.44

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-3.7

REVEL

Benign

0.13

Sift

Benign

0.072

Sift4G

Benign

0.14

Polyphen

0.28

Vest4

0.10

MutPred

0.79

Gain of MoRF binding (P = 0.0822)

MVP

0.38

MPC

0.064

ClinPred

0.42

GERP RS

2.5

Varity_R

0.10

gMVP

0.25

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.22

Position offset: 31

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over