NM_001321967.2:c.831+3748A>G

Variant names:

• chr10-87763925-T-C
• rs1923260
• NM_001321967.2:c.831+3748A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001321967.2(ATAD1):​c.831+3748A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 151,946 control chromosomes in the GnomAD database, including 6,762 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.29 (6762 hom., cov: 31)
• Consequence: ATAD1 NM_001321967.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.118
• Publications: 1 publications found

Genes affected

ATAD1 (HGNC:25903): (ATPase family AAA domain containing 1) Predicted to enable ATP binding activity and transmembrane protein dislocase activity. Involved in extraction of mislocalized protein from mitochondrial outer membrane. Located in mitochondrial outer membrane and peroxisomal membrane. Implicated in hyperekplexia 4. [provided by Alliance of Genome Resources, Apr 2022]

ATAD1 Gene-Disease associations (from GenCC):

• hyperekplexia 4

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• hereditary hyperekplexia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321967.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATAD1	NM_001321967.2	MANE Select	c.831+3748A>G		intron	N/A	NP_001308896.1
	ATAD1	NM_032810.4		c.831+3748A>G		intron	N/A	NP_116199.2
	ATAD1	NM_001321968.2		c.741+3748A>G		intron	N/A	NP_001308897.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATAD1	ENST00000680024.1	MANE Select	c.831+3748A>G		intron	N/A	ENSP00000506333.1
	ATAD1	ENST00000328142.3	TSL:1	c.831+3748A>G		intron	N/A	ENSP00000339016.2
	ATAD1	ENST00000308448.11	TSL:2	c.831+3748A>G		intron	N/A	ENSP00000339017.4

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44578 AN: 151828 Hom.: 6751 Cov.: 31

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.286

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.294 AC: 44607 AN: 151946 Hom.: 6762 Cov.: 31 AF XY: 0.292 AC XY: 21678 AN XY: 74254

African (AFR) AF: 0.293 AC: 12146 AN: 41408

American (AMR) AF: 0.269 AC: 4112 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 984 AN: 3468

East Asian (EAS) AF: 0.157 AC: 811 AN: 5176

South Asian (SAS) AF: 0.245 AC: 1180 AN: 4810

European-Finnish (FIN) AF: 0.317 AC: 3342 AN: 10536

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.310 AC: 21045 AN: 67976

Other (OTH) AF: 0.294 AC: 621 AN: 2110

Alfa AF: 0.303 Hom.: 918

Bravo AF: 0.290

Asia WGS AF: 0.236 AC: 819 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.7
DANN	Benign	0.43
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1923260; hg19: chr10-89523682;