chr1-1472084-A-G

Variant names:

• chr1-1472084-A-G
• rs1639353517
• NM_031921.6:c.200A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_031921.6(ATAD3B):​c.200A>G​(p.His67Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000172 in 1,165,404 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000075 (0 hom., cov: 24)
  • Exomes 𝑓: 9.7e-7 (0 hom.)
• Consequence: ATAD3B NM_031921.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.04
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03328821).

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.200A>G	p.His67Arg	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.200A>G	p.His67Arg	missense	Exon 1 of 16	ENSP00000500094.1	Q5T9A4-1
	ATAD3B	ENST00000308647.8	TSL:1	c.200A>G	p.His67Arg	missense	Exon 1 of 14	ENSP00000311766.8	A0A5K1VW56
	ATAD3B	ENST00000940534.1		c.200A>G	p.His67Arg	missense	Exon 1 of 17	ENSP00000610593.1

Frequencies

GnomAD3 genomes AF: 0.00000749 AC: 1 AN: 133560 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000751

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 9.69e-7 AC: 1 AN: 1031844 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 489110

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 19136

American (AMR) AF: 0.00 AC: 0 AN: 5640

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11704

East Asian (EAS) AF: 0.0000666 AC: 1 AN: 15024

South Asian (SAS) AF: 0.00 AC: 0 AN: 24888

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25300

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2530

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 888524

Other (OTH) AF: 0.00 AC: 0 AN: 39098

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00000749 AC: 1 AN: 133560 Hom.: 0 Cov.: 24 AF XY: 0.0000155 AC XY: 1 AN XY: 64504

African (AFR) AF: 0.00 AC: 0 AN: 31854

American (AMR) AF: 0.0000751 AC: 1 AN: 13316

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3382

East Asian (EAS) AF: 0.00 AC: 0 AN: 3494

South Asian (SAS) AF: 0.00 AC: 0 AN: 3950

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8688

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 300

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65850

Other (OTH) AF: 0.00 AC: 0 AN: 1860

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	Benign	0.094
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	21
DANN	Benign	0.74
DEOGEN2	Benign	0.0048	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.91	D
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.033	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.42	N
PhyloP100		5.0
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	0.64	N
REVEL	Benign	0.036
Sift	Benign	0.73	T
Sift4G	Benign	0.60	T
Polyphen		0.0030	B
Vest4		0.18
MutPred		0.21		Gain of MoRF binding (P = 0.012)
MVP		0.36
MPC		1.0
ClinPred		0.11	T
GERP RS		2.6
PromoterAI		0.011	Neutral
Varity_R		0.064
gMVP		0.023
Mutation Taster		=96/4	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: rs1639353517; hg19: chr1-1407464;