1-1512376-G-T

Variant names:

• chr1-1512376-G-T
• rs1240736
• NM_001170535.3:c.108G>T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001170535.3(ATAD3A):​c.108G>T​(p.Gly36Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000029 in 1,239,676 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. Synonymous variant affecting the same amino acid position (i.e. G36G) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.000080 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000022 (0 hom.)
• Consequence: ATAD3A NM_001170535.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0330

Genes affected

ATAD3A (HGNC:25567): (ATPase family AAA domain containing 3A) This gene encodes a ubiquitously expressed mitochondrial membrane protein that contributes to mitochondrial dynamics, nucleoid organization, protein translation, cell growth, and cholesterol metabolism. This gene is a member of the ATPase family AAA-domain containing 3 gene family which, in humans, includes two other paralogs. Naturally occurring mutations in this gene are associated with distinct neurological syndromes including Harel-Yoon syndrome. High-level expression of this gene is associated with poor survival in breast cancer patients. A homozygous knockout of the orthologous gene in mice results in embryonic lethality at day 7.5 due to growth retardation and defective development of the trophoblast lineage. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2017]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP7: Synonymous conserved (PhyloP=-0.033 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATAD3A	NM_001170535.3	c.108G>T	p.Gly36Gly	synonymous_variant	Exon 1 of 16	ENST00000378756.8	NP_001164006.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATAD3A	ENST00000378756.8	c.108G>T	p.Gly36Gly	synonymous_variant	Exon 1 of 16	1	NM_001170535.3	ENSP00000368031.3

Frequencies

GnomAD3 genomes AF: 0.0000796 AC: 12 AN: 150666 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000132

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: 0.000148

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000220 AC: 24 AN: 1089010 Hom.: 0 Cov.: 31 AF XY: 0.0000251 AC XY: 13 AN XY: 517616

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000125

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: 0.0000228

Gnomad4 OTH exome AF: 0.0000233

GnomAD4 genome AF: 0.0000796 AC: 12 AN: 150666 Hom.: 0 Cov.: 30 AF XY: 0.0000680 AC XY: 5 AN XY: 73532

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000132

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000148

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.5
DANN	Benign	0.38

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

LitVar

Other links and lift over

dbSNP: rs1240736; hg19: chr1-1447756;