Variant chr21-44143324-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_004649.8(GATD3):c.641A>G(p.Lys214Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GATD3
NM_004649.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.32

Variant links:

Genes affected

GATD3 (HGNC:1273): (glutamine amidotransferase class 1 domain containing 3) This gene encodes a potential mitochondrial protein that is a member of the DJ-1/PfpI gene family. This protein is overexpressed in fetal Down syndrome brain. Alternate splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

GATD3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13154471).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
GATD3	NM_004649.8 linkuse as main transcript	c.641A>G	p.Lys214Arg	missense_variant	6/7	ENST00000291577.11	NP_004640.4
GATD3	NM_198155.5 linkuse as main transcript	c.548A>G	p.Lys183Arg	missense_variant	5/6		NP_937798.4
GATD3	XM_017028479.2 linkuse as main transcript	c.383A>G	p.Lys128Arg	missense_variant	5/6		XP_016883968.1
GATD3	NR_135220.2 linkuse as main transcript	n.603A>G		non_coding_transcript_exon_variant	5/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GATD3	ENST00000291577.11 linkuse as main transcript	c.641A>G	p.Lys214Arg	missense_variant	6/7	1	NM_004649.8	ENSP00000291577	P1	P0DPI2-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

6760

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000250

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

249976

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135312

show subpopulations

Gnomad AFR exome

AF:

0.000185

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

30732

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

15556

Gnomad4 AFR exome

AF:

0.00

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

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

AF:

0.00

AC:

AN:

6808

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

3116

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000247

AC:

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

Jan 31, 2024

The c.641A>G (p.K214R) alteration is located in exon 6 (coding exon 6) of the C21orf33 gene. This alteration results from a A to G substitution at nucleotide position 641, causing the lysine (K) at amino acid position 214 to be replaced by an arginine (R). 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

Benign

0.090

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.071

Eigen_PC

Benign

-0.057

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.85

D;T;T

M_CAP

Benign

0.039

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.93

N;N

PROVEAN

Benign

-1.1

N;N;.

REVEL

Benign

0.019

Sift

Benign

0.10

T;T;.

Sift4G

Benign

0.24

T;T;.

Vest4

0.33

MVP

0.89

MPC

0.057

ClinPred

0.060

GERP RS

3.5

Varity_R

0.051

gMVP

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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