1-1485777-G-A

Position:

• chr1-1485777-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_031921.6(ATAD3B):​c.907-5G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00835 in 1,610,472 control chromosomes in the GnomAD database, including 308 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.016 (72 hom., cov: 32)
  • Exomes 𝑓: 0.0075 (236 hom.)
• Consequence: ATAD3B NM_031921.6 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.3048
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.28

Genes affected

ATAD3B (HGNC:24007): (ATPase family AAA domain containing 3B) The protein encoded by this gene is localized to the mitochondrial inner membrane, where it can bind to a highly-related protein, ATAD3A. ATAD3A appears to interact with matrix nucleoid complexes, and the encoded protein negatively regulates that interaction. This gene is expressed almost exclusively in pluripotent embryonic stem cells and some cancer cells. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0164 (2485/151910) while in subpopulation AFR AF= 0.041 (1697/41440). AF 95% confidence interval is 0.0393. There are 72 homozygotes in gnomad4. There are 1239 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 72 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATAD3B	NM_031921.6	c.907-5G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000673477.1	NP_114127.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATAD3B	ENST00000673477.1	c.907-5G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NM_031921.6	ENSP00000500094	P1

Frequencies

GnomAD3 genomes AF: 0.0164 AC: 2482 AN: 151794 Hom.: 72 Cov.: 32

Gnomad AFR AF: 0.0410

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00539

Gnomad ASJ AF: 0.00606

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.00208

Gnomad FIN AF: 0.0144

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.00720

Gnomad OTH AF: 0.0149

GnomAD3 exomes AF: 0.00690 AC: 1711 AN: 248126 Hom.: 28 AF XY: 0.00638 AC XY: 860 AN XY: 134696

Gnomad AFR exome AF: 0.0293

Gnomad AMR exome AF: 0.00444

Gnomad ASJ exome AF: 0.00742

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00219

Gnomad FIN exome AF: 0.0154

Gnomad NFE exome AF: 0.00529

Gnomad OTH exome AF: 0.00661

GnomAD4 exome AF: 0.00751 AC: 10958 AN: 1458562 Hom.: 236 Cov.: 33 AF XY: 0.00715 AC XY: 5188 AN XY: 725584

Gnomad4 AFR exome AF: 0.0359

Gnomad4 AMR exome AF: 0.00466

Gnomad4 ASJ exome AF: 0.00801

Gnomad4 EAS exome AF: 0.000151

Gnomad4 SAS exome AF: 0.00215

Gnomad4 FIN exome AF: 0.0158

Gnomad4 NFE exome AF: 0.00715

Gnomad4 OTH exome AF: 0.00632

GnomAD4 genome AF: 0.0164 AC: 2485 AN: 151910 Hom.: 72 Cov.: 32 AF XY: 0.0167 AC XY: 1239 AN XY: 74238

Gnomad4 AFR AF: 0.0410

Gnomad4 AMR AF: 0.00538

Gnomad4 ASJ AF: 0.00606

Gnomad4 EAS AF: 0.000388

Gnomad4 SAS AF: 0.00209

Gnomad4 FIN AF: 0.0144

Gnomad4 NFE AF: 0.00717

Gnomad4 OTH AF: 0.0147

Alfa AF: 0.00571 Hom.: 1

Bravo AF: 0.0172

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	18
DANN	Benign	0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.30
dbscSNV1_RF	Benign	0.54
SpliceAI score (max)		0.99		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.99		Position offset: 2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1622213; hg19: chr1-1421157;