21-44137261-C-T

Position:

• chr21-44137261-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP6_Very_Strong BP7

The NM_004649.8(GATD3):​c.393C>T​(p.Ala131=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GATD3 NM_004649.8 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.93

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]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BP6: Variant 21-44137261-C-T is Benign according to our data. Variant chr21-44137261-C-T is described in ClinVar as [Benign]. Clinvar id is 775444.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.93 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GATD3	NM_004649.8	c.393C>T	p.Ala131=	synonymous_variant	4/7	ENST00000291577.11	NP_004640.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GATD3	ENST00000291577.11	c.393C>T	p.Ala131=	synonymous_variant	4/7	1	NM_004649.8	ENSP00000291577	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 0 Hom.: 0 Cov.: 0 FAILED QC

GnomAD3 exomes AF: 0.00463 AC: 1164 AN: 251490 Hom.: 14 AF XY: 0.00451 AC XY: 613 AN XY: 135920

Gnomad AFR exome AF: 0.00794

Gnomad AMR exome AF: 0.00486

Gnomad ASJ exome AF: 0.0430

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00137

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.00312

Gnomad OTH exome AF: 0.00554

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 AMR exome AF: 0.00

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 0

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

Alfa AF: 0.00676 Hom.: 10

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.00365

EpiControl AF: 0.00397

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 06, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	15
DANN	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs61737073; hg19: chr21-45557143;