1-1472084-A-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031921.6(ATAD3B):​c.200A>T​(p.His67Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000194 in 1,031,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H67R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000019 (0 hom.)
• Consequence: ATAD3B NM_031921.6 missense
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0733214).

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>T	p.His67Leu	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>T	p.His67Leu	missense	Exon 1 of 16	ENSP00000500094.1	Q5T9A4-1
	ATAD3B	ENST00000308647.8	TSL:1	c.200A>T	p.His67Leu	missense	Exon 1 of 14	ENSP00000311766.8	A0A5K1VW56
	ATAD3B	ENST00000940534.1		c.200A>T	p.His67Leu	missense	Exon 1 of 17	ENSP00000610593.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 0.00000194 AC: 2 AN: 1031844 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 489110

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: 0.00 AC: 0 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: 0.00000225 AC: 2 AN: 888524

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

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	23
DANN	Benign	0.92
DEOGEN2	Benign	0.034	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.64	D
LIST_S2	Uncertain	0.89	D
M_CAP	Uncertain	0.25	D
MetaRNN	Benign	0.073	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		5.0
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.040
Sift	Benign	0.28	T
Sift4G	Benign	0.30	T
Polyphen		0.13	B
Vest4		0.23
MutPred		0.16		Loss of ubiquitination at K72 (P = 0.0434)
MVP		0.55
MPC		1.0
ClinPred		0.53	D
GERP RS		2.6
PromoterAI		0.44	Neutral
Varity_R		0.13
gMVP		0.065
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;