Genetic Variant GATD1:p.Ala163Pro (chr11-771390-C-G) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_182612.4(GATD1):c.487G>C(p.Ala163Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. A163S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GATD1
NM_182612.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.52

Publications

0 publications found

Variant links:

Genes affected

GATD1 (HGNC:26616): (glutamine amidotransferase class 1 domain containing 1) Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

GATD1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.772

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182612.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GATD1	NM_182612.4	MANE Select	c.487G>C	p.Ala163Pro	missense	Exon 6 of 8	NP_872418.1	Q8NB37-1
GATD1	NM_001318821.2		c.487G>C	p.Ala163Pro	missense	Exon 6 of 7	NP_001305750.1
GATD1	NM_001318824.2		c.379G>C	p.Ala127Pro	missense	Exon 5 of 7	NP_001305753.1	Q8NB37-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GATD1	ENST00000319863.13	TSL:1 MANE Select	c.487G>C	p.Ala163Pro	missense	Exon 6 of 8	ENSP00000321691.8	Q8NB37-1
GATD1	ENST00000397472.6	TSL:1	c.487G>C	p.Ala163Pro	missense	Exon 6 of 8	ENSP00000380612.2	Q8NB37-2
GATD1	ENST00000524550.5	TSL:1	c.379G>C	p.Ala127Pro	missense	Exon 5 of 7	ENSP00000431183.1	Q8NB37-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

199384

AF XY:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1417578

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

701438

African (AFR)

AF:

0.00

AC:

AN:

32206

American (AMR)

AF:

0.00

AC:

AN:

38844

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22932

East Asian (EAS)

AF:

0.00

AC:

AN:

39350

South Asian (SAS)

AF:

0.00

AC:

AN:

79438

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49468

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5544

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1091412

Other (OTH)

AF:

0.00

AC:

AN:

58384

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Uncertain

0.040

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.042

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.82

M_CAP

Uncertain

0.23

MetaRNN

Pathogenic

0.77

MetaSVM

Benign

-0.31

PhyloP100

6.5

PrimateAI

Uncertain

0.73

PROVEAN

Uncertain

-2.9

REVEL

Uncertain

0.58

Sift

Benign

0.060

Sift4G

Uncertain

0.022

Polyphen

0.72

Vest4

0.71

MutPred

0.46

Gain of relative solvent accessibility (P = 0.0023)

MVP

0.35

MPC

0.48

ClinPred

0.95

GERP RS

4.4

PromoterAI

0.013

Neutral

(source)

Varity_R

0.51

gMVP

0.50

Mutation Taster

=50/50

(source)

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

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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