1-1454462-C-A

Variant names:

• chr1-1454462-C-A
• NM_001039211.3:c.340C>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001039211.3(ATAD3C):​c.340C>A​(p.Arg114Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,457,750 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R114C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ATAD3C NM_001039211.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.885

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.801

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATAD3C	NM_001039211.3	c.340C>A	p.Arg114Ser	missense_variant	Exon 4 of 12	ENST00000378785.7	NP_001034300.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATAD3C	ENST00000378785.7	c.340C>A	p.Arg114Ser	missense_variant	Exon 4 of 12	2	NM_001039211.3	ENSP00000368062.2
ATAD3C	ENST00000475091.2	c.223-998C>A		intron_variant	Intron 4 of 5	5		ENSP00000464661.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1457750 Hom.: 0 Cov.: 33 AF XY: 0.00000276 AC XY: 2 AN XY: 725086

Gnomad4 AFR exome AF: 0.0000300

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000190

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.030
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.044	T
Eigen	Benign	0.19
Eigen_PC	Benign	-0.046
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.83	T
M_CAP	Uncertain	0.10	D
MetaRNN	Pathogenic	0.80	D
MetaSVM	Pathogenic	0.93	D
MutationAssessor	Pathogenic	3.3	M
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-5.7	D
REVEL	Pathogenic	0.69
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.82
MutPred		0.47		Loss of MoRF binding (P = 0.0125);
MVP		0.83
MPC		0.67
ClinPred		0.99	D
GERP RS		1.4
Varity_R		0.91
gMVP		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-1389842;