chr1-1472082-G-C

Variant names:

• chr1-1472082-G-C
• rs1272515675
• NM_031921.6:c.198G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_031921.6(ATAD3B):​c.198G>C​(p.Glu66Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00015 in 139,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E66G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 25)
  • Exomes 𝑓: 0.00014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ATAD3B NM_031921.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.88
• Publications: 0 publications found

Genes affected

ATAD3B (HGNC:24007): (ATPase family AAA domain containing 3B) The protein encoded by this gene is localized to the mitochondrial inner membrane, where it can bind to a highly-related protein, ATAD3A. ATAD3A appears to interact with matrix nucleoid complexes, and the encoded protein negatively regulates that interaction. This gene is expressed almost exclusively in pluripotent embryonic stem cells and some cancer cells. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2015]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.17635229).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031921.6. 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
	ATAD3B	NM_031921.6	MANE Select	c.198G>C	p.Glu66Asp	missense	Exon 1 of 16	NP_114127.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATAD3B	ENST00000673477.1	MANE Select	c.198G>C	p.Glu66Asp	missense	Exon 1 of 16	ENSP00000500094.1	Q5T9A4-1
	ATAD3B	ENST00000308647.8	TSL:1	c.198G>C	p.Glu66Asp	missense	Exon 1 of 14	ENSP00000311766.8	A0A5K1VW56
	ATAD3B	ENST00000940534.1		c.198G>C	p.Glu66Asp	missense	Exon 1 of 17	ENSP00000610593.1

Frequencies

GnomAD3 genomes AF: 0.000150 AC: 21 AN: 139602 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.0000286

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000141

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000256

Gnomad OTH AF: 0.000515

GnomAD2 exomes AF: 0.00 AC: 0 AN: 4234 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000141 AC: 149 AN: 1056220 Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 67 AN XY: 500564

African (AFR) AF: 0.00 AC: 0 AN: 20930

American (AMR) AF: 0.000298 AC: 2 AN: 6722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12340

East Asian (EAS) AF: 0.00 AC: 0 AN: 20900

South Asian (SAS) AF: 0.0000810 AC: 2 AN: 24704

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2654

European-Non Finnish (NFE) AF: 0.000156 AC: 140 AN: 899542

Other (OTH) AF: 0.000122 AC: 5 AN: 40836

GnomAD4 genome AF: 0.000150 AC: 21 AN: 139672 Hom.: 0 Cov.: 25 AF XY: 0.000118 AC XY: 8 AN XY: 67870

African (AFR) AF: 0.0000286 AC: 1 AN: 35026

American (AMR) AF: 0.000141 AC: 2 AN: 14216

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3400

East Asian (EAS) AF: 0.00 AC: 0 AN: 3996

South Asian (SAS) AF: 0.00 AC: 0 AN: 4262

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9370

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 282

European-Non Finnish (NFE) AF: 0.000256 AC: 17 AN: 66286

Other (OTH) AF: 0.000511 AC: 1 AN: 1958

Alfa AF: 0.00 Hom.: 0

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	Uncertain	0.44
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	21
DANN	Benign	0.90
DEOGEN2	Benign	0.0085	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.84	T
M_CAP	Pathogenic	0.90	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	-0.33	N
PhyloP100		3.9
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-1.6	N
REVEL	Uncertain	0.31
Sift	Benign	0.51	T
Sift4G	Benign	0.53	T
Polyphen		0.017	B
Vest4		0.071
MutPred		0.24		Loss of helix (P = 0.0017)
MVP		0.67
MPC		0.88
ClinPred		0.68	D
GERP RS		2.6
PromoterAI		-0.039	Neutral
Varity_R		0.16
gMVP		0.068
Mutation Taster		=292/8	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: rs1272515675; hg19: chr1-1407462; COSMIC: COSV105823847;