1-1512268-C-T

Variant names:

• chr1-1512268-C-T
• rs1641217439
• NM_001170535.3:c.-1C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001170535.3(ATAD3A):​c.-1C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000713 in 1,121,512 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000071 (0 hom.)
• Consequence: ATAD3A NM_001170535.3 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.974
• Publications: 0 publications found

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]

ATAD3A Gene-Disease associations (from GenCC):

• Harel-Yoon syndrome

  Inheritance: AD, AR, SD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Illumina
• pontocerebellar hypoplasia, hypotonia, and respiratory insufficiency syndrome, neonatal lethal

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, PanelApp Australia

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001170535.3. 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
	ATAD3A	NM_001170535.3	MANE Select	c.-1C>T		5_prime_UTR	Exon 1 of 16	NP_001164006.1	Q9NVI7-2
	ATAD3A	NM_018188.5		c.-1C>T		5_prime_UTR	Exon 1 of 16	NP_060658.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATAD3A	ENST00000378756.8	TSL:1 MANE Select	c.-1C>T		5_prime_UTR	Exon 1 of 16	ENSP00000368031.3	Q9NVI7-2
	ATAD3A	ENST00000378755.9	TSL:2	c.-1C>T		5_prime_UTR	Exon 1 of 16	ENSP00000368030.5	Q9NVI7-1
	ATAD3A	ENST00000936382.1		c.-1C>T		5_prime_UTR	Exon 1 of 16	ENSP00000606441.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000713 AC: 8 AN: 1121512 Hom.: 0 Cov.: 30 AF XY: 0.00000561 AC XY: 3 AN XY: 535132

African (AFR) AF: 0.0000420 AC: 1 AN: 23794

American (AMR) AF: 0.00 AC: 0 AN: 13436

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14374

East Asian (EAS) AF: 0.0000355 AC: 1 AN: 28138

South Asian (SAS) AF: 0.00 AC: 0 AN: 24020

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33822

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2924

European-Non Finnish (NFE) AF: 0.00000641 AC: 6 AN: 936678

Other (OTH) AF: 0.00 AC: 0 AN: 44326

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	14
DANN	Benign	0.95
PhyloP100		0.97
PromoterAI		0.023	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1641217439; hg19: chr1-1447648;