rs1854143524

Variant names:

• chr10-87754723-T-A
• rs1854143524
• NM_001321967.2:c.1050A>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001321967.2(ATAD1):​c.1050A>T​(p.Ala350Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ATAD1 NM_001321967.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.60
• Publications: 0 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: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 10-87754723-T-A is Benign according to our data. Variant chr10-87754723-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2798901.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.6 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATAD1	NM_001321967.2	MANE Select	c.1050A>T	p.Ala350Ala	synonymous	Exon 10 of 10	NP_001308896.1	Q8NBU5-1
	ATAD1	NM_032810.4		c.1050A>T	p.Ala350Ala	synonymous	Exon 10 of 10	NP_116199.2
	ATAD1	NM_001321968.2		c.960A>T	p.Ala320Ala	synonymous	Exon 9 of 9	NP_001308897.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATAD1	ENST00000680024.1	MANE Select	c.1050A>T	p.Ala350Ala	synonymous	Exon 10 of 10	ENSP00000506333.1	Q8NBU5-1
	ATAD1	ENST00000328142.3	TSL:1	c.1050A>T	p.Ala350Ala	synonymous	Exon 9 of 9	ENSP00000339016.2	Q8NBU5-1
	ATAD1	ENST00000944904.1		c.1074A>T	p.Ala358Ala	synonymous	Exon 11 of 11	ENSP00000614963.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

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	-0.66
CADD	Benign	5.4
DANN	Benign	0.53
PhyloP100		-1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs1854143524; hg19: chr10-89514480;