1-1452074-A-C

Variant names:

• chr1-1452074-A-C
• rs1570141966
• NM_001039211.3:c.104A>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001039211.3(ATAD3C):​c.104A>C​(p.Gln35Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ATAD3C NM_001039211.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.46
• Publications: 0 publications found

Genes affected

ATAD3C (HGNC:32151): (ATPase family AAA domain containing 3C) Predicted to enable zinc ion binding activity. Predicted to be involved in mitochondrion organization. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ATAD3C Gene-Disease associations (from GenCC):

• pontocerebellar hypoplasia, hypotonia, and respiratory insufficiency syndrome, neonatal lethal

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039211.3. 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
	ATAD3C	NM_001039211.3	MANE Select	c.104A>C	p.Gln35Pro	missense	Exon 2 of 12	NP_001034300.2	Q5T2N8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATAD3C	ENST00000378785.7	TSL:2 MANE Select	c.104A>C	p.Gln35Pro	missense	Exon 2 of 12	ENSP00000368062.2	Q5T2N8
	ATAD3C	ENST00000475091.2	TSL:5	c.104A>C	p.Gln35Pro	missense	Exon 3 of 6	ENSP00000464661.1	J3QSF3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.030
CADD	Benign	23
DANN	Benign	0.66
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.019
Eigen_PC	Benign	-0.049
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.38	T
M_CAP	Uncertain	0.099	D
MetaRNN	Uncertain	0.67	D
MetaSVM	Uncertain	0.12	D
MutationAssessor	Benign	1.5	L
PhyloP100		7.5
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.55
Sift	Benign	0.11	T
Sift4G	Uncertain	0.046	D
Polyphen		0.87	P
Vest4		0.88
MutPred		0.31		Gain of helix (P = 0.0325)
MVP		0.88
MPC		0.43
ClinPred		0.79	D
GERP RS		2.6
Varity_R		0.95
gMVP		0.58
Mutation Taster		=92/8	polymorphism

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: rs1570141966; hg19: chr1-1387454;