rs941093789

Variant names:

• chr1-1472081-A-G
• rs941093789
• NM_031921.6:c.197A>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_031921.6(ATAD3B):​c.197A>G​(p.Glu66Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000236 in 1,167,170 control chromosomes in the GnomAD database, including 2 homozygotes. 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. E66D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00027 (0 hom., cov: 24)
  • Exomes 𝑓: 0.00023 (2 hom.)
• Consequence: ATAD3B NM_031921.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.29
• 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 -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.35011405).
• BS2: High Homozygotes in GnomAdExome4 at 2 gene

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.197A>G	p.Glu66Gly	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.197A>G	p.Glu66Gly	missense	Exon 1 of 16	ENSP00000500094.1	Q5T9A4-1
	ATAD3B	ENST00000308647.8	TSL:1	c.197A>G	p.Glu66Gly	missense	Exon 1 of 14	ENSP00000311766.8	A0A5K1VW56
	ATAD3B	ENST00000940534.1		c.197A>G	p.Glu66Gly	missense	Exon 1 of 17	ENSP00000610593.1

Frequencies

GnomAD3 genomes AF: 0.000271 AC: 37 AN: 136680 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.0000298

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00221

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000243

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000462 AC: 2 AN: 4332 AF XY: 0.000848

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad FIN exome AF: 0.000585

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000231 AC: 238 AN: 1030490 Hom.: 2 Cov.: 32 AF XY: 0.000248 AC XY: 121 AN XY: 487450

African (AFR) AF: 0.0000514 AC: 1 AN: 19456

American (AMR) AF: 0.00 AC: 0 AN: 5796

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11724

East Asian (EAS) AF: 0.00 AC: 0 AN: 15738

South Asian (SAS) AF: 0.00 AC: 0 AN: 23074

European-Finnish (FIN) AF: 0.00304 AC: 77 AN: 25342

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2516

European-Non Finnish (NFE) AF: 0.000175 AC: 155 AN: 887758

Other (OTH) AF: 0.000128 AC: 5 AN: 39086

GnomAD4 genome AF: 0.000271 AC: 37 AN: 136680 Hom.: 0 Cov.: 24 AF XY: 0.000332 AC XY: 22 AN XY: 66184

African (AFR) AF: 0.0000298 AC: 1 AN: 33570

American (AMR) AF: 0.00 AC: 0 AN: 13890

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3386

East Asian (EAS) AF: 0.00 AC: 0 AN: 3752

South Asian (SAS) AF: 0.00 AC: 0 AN: 4056

European-Finnish (FIN) AF: 0.00221 AC: 20 AN: 9038

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 302

European-Non Finnish (NFE) AF: 0.000243 AC: 16 AN: 65918

Other (OTH) AF: 0.00 AC: 0 AN: 1890

Alfa AF: 0.000270 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	0.52
BayesDel_addAF	Uncertain	0.029	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.91	D
M_CAP	Pathogenic	0.97	D
MetaRNN	Benign	0.35	T
MetaSVM	Uncertain	0.35	D
MutationAssessor	Benign	2.0	M
PhyloP100		8.3
PrimateAI	Pathogenic	0.88	D
PROVEAN	Pathogenic	-5.0	D
REVEL	Uncertain	0.57
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.056	T
Polyphen		0.93	P
Vest4		0.15
MutPred		0.31		Loss of helix (P = 3e-04)
MVP		0.85
MPC		2.1
ClinPred		0.46	T
GERP RS		2.6
PromoterAI		-0.031	Neutral
Varity_R		0.50
gMVP		0.097
Mutation Taster		=85/15	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: rs941093789; hg19: chr1-1407461;