Genetic Variant ATAD3C:p.Ala91Val (chr1-1454394-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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. A91E) 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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.16

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATAD3C	NM_001039211.3 link	c.272C>T	p.Ala91Val	missense_variant	Exon 4 of 12	ENST00000378785.7	NP_001034300.2	Q5T2N8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATAD3C	ENST00000378785.7 link	c.272C>T	p.Ala91Val	missense_variant	Exon 4 of 12	2	NM_001039211.3	ENSP00000368062.2		Q5T2N8
ATAD3C	ENST00000475091.2 link	c.223-1066C>T		intron_variant	Intron 4 of 5	5		ENSP00000464661.1		J3QSF3

Frequencies

GnomAD3 genomes

AF:

0.0196

AC:

2975

AN:

151908

Hom.:

109

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.00503

AC:

1161

AN:

230612

Hom.:

AF XY:

0.00356

AC XY:

447

AN XY:

125610

show subpopulations

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 SAS exome

AF:

0.000210

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.:

Cov.:

AF XY:

0.00162

AC XY:

1171

AN XY:

721218

show subpopulations

Gnomad4 AFR exome

AF:

0.0688

Gnomad4 AMR exome

AF:

0.00426

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000179

Gnomad4 SAS exome

AF:

0.000177

Gnomad4 FIN exome

AF:

0.0000195

Gnomad4 NFE exome

AF:

0.0000379

Gnomad4 OTH exome

AF:

0.00413

GnomAD4 genome

AF:

0.0196

AC:

2987

AN:

152024

Hom.:

109

Cov.:

AF XY:

0.0198

AC XY:

1470

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.0678

Gnomad4 AMR

AF:

0.00826

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.0186

Alfa

AF:

0.00104

Hom.:

Bravo

AF:

0.0226

ExAC

AF:

0.00600

AC:

719

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.12

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.028

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.56

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.94

MetaRNN

Benign

0.0071

MetaSVM

Uncertain

-0.020

MutationAssessor

Uncertain

2.1

PrimateAI

Uncertain

0.67

PROVEAN

Uncertain

-3.1

REVEL

Uncertain

0.48

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.016

Polyphen

0.97

Vest4

0.73

MVP

0.87

MPC

0.34

ClinPred

0.060

GERP RS

1.2

Varity_R

0.47

gMVP

0.25

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over