1-1454394-C-T

Variant names:

• chr1-1454394-C-T
• rs182547232
• NM_001039211.3:c.272C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001039211.3(ATAD3C):​c.272C>T​(p.Ala91Val) variant causes a missense change. The variant allele was found at a frequency of 0.00361 in 1,603,002 control chromosomes in the GnomAD database, including 195 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A91G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.020 (109 hom., cov: 31)
  • Exomes 𝑓: 0.0019 (86 hom.)
• Consequence: ATAD3C NM_001039211.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 5.16
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007075608).
• BP6: Variant 1-1454394-C-T is Benign according to our data. Variant chr1-1454394-C-T is described in ClinVar as Benign. ClinVar VariationId is 1253304.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0657 is higher than 0.05.

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.272C>T	p.Ala91Val	missense	Exon 4 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.272C>T	p.Ala91Val	missense	Exon 4 of 12	ENSP00000368062.2	Q5T2N8
	ATAD3C	ENST00000475091.2	TSL:5	c.223-1066C>T		intron	N/A	ENSP00000464661.1	J3QSF3

Frequencies

GnomAD3 genomes AF: 0.0196 AC: 2975 AN: 151908 Hom.: 109 Cov.: 31

Gnomad AFR AF: 0.0678

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00827

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.0183

GnomAD2 exomes AF: 0.00503 AC: 1161 AN: 230612 AF XY: 0.00356

Gnomad AFR exome AF: 0.0724

Gnomad AMR exome AF: 0.00353

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000179

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000579

Gnomad OTH exome AF: 0.00195

GnomAD4 exome AF: 0.00193 AC: 2798 AN: 1450978 Hom.: 86 Cov.: 33 AF XY: 0.00162 AC XY: 1171 AN XY: 721218

African (AFR) AF: 0.0688 AC: 2288 AN: 33238

American (AMR) AF: 0.00426 AC: 186 AN: 43694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25934

East Asian (EAS) AF: 0.000179 AC: 7 AN: 39186

South Asian (SAS) AF: 0.000177 AC: 15 AN: 84706

European-Finnish (FIN) AF: 0.0000195 AC: 1 AN: 51178

Middle Eastern (MID) AF: 0.00261 AC: 12 AN: 4596

European-Non Finnish (NFE) AF: 0.0000379 AC: 42 AN: 1108646

Other (OTH) AF: 0.00413 AC: 247 AN: 59800

GnomAD4 genome AF: 0.0196 AC: 2987 AN: 152024 Hom.: 109 Cov.: 31 AF XY: 0.0198 AC XY: 1470 AN XY: 74314

African (AFR) AF: 0.0678 AC: 2811 AN: 41446

American (AMR) AF: 0.00826 AC: 126 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5168

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4798

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 67970

Other (OTH) AF: 0.0186 AC: 39 AN: 2102

Alfa AF: 0.00363 Hom.: 2

Bravo AF: 0.0226

ExAC AF: 0.00600 AC: 719

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.56
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.94	D
MetaRNN	Benign	0.0071	T
MetaSVM	Uncertain	-0.020	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		5.2
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-3.1	D
REVEL	Uncertain	0.48
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.016	D
Polyphen		0.97	D
Vest4		0.73
MVP		0.87
MPC		0.34
ClinPred		0.060	T
GERP RS		1.2
Varity_R		0.47
gMVP		0.25
Mutation Taster		=92/8	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: rs182547232; hg19: chr1-1389774; COSMIC: COSV66482525;