chr1-1471946-C-T

Variant names:

• chr1-1471946-C-T
• NM_031921.6:c.62C>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.62C>T​(p.Pro21Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000046 in 1,087,714 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: not found (cov: 30)
  • Exomes 𝑓: 0.0000046 (0 hom.)
• Consequence: ATAD3B NM_031921.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.40
• 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=0.11836964).

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.62C>T	p.Pro21Leu	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.62C>T	p.Pro21Leu	missense	Exon 1 of 16	ENSP00000500094.1	Q5T9A4-1
	ATAD3B	ENST00000308647.8	TSL:1	c.62C>T	p.Pro21Leu	missense	Exon 1 of 14	ENSP00000311766.8	A0A5K1VW56
	ATAD3B	ENST00000940534.1		c.62C>T	p.Pro21Leu	missense	Exon 1 of 17	ENSP00000610593.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000460 AC: 5 AN: 1087714 Hom.: 0 Cov.: 30 AF XY: 0.00000194 AC XY: 1 AN XY: 514544

African (AFR) AF: 0.00 AC: 0 AN: 22442

American (AMR) AF: 0.00 AC: 0 AN: 8136

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13962

East Asian (EAS) AF: 0.00 AC: 0 AN: 25584

South Asian (SAS) AF: 0.0000509 AC: 1 AN: 19660

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33272

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2886

European-Non Finnish (NFE) AF: 0.00000435 AC: 4 AN: 918616

Other (OTH) AF: 0.00 AC: 0 AN: 43156

GnomAD4 genome Cov.: 30

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	0.087
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	20
DANN	Benign	0.90
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.69	T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M
PhyloP100		2.4
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.12
Sift	Benign	0.083	T
Sift4G	Uncertain	0.016	D
Polyphen		0.0010	B
Vest4		0.15
MutPred		0.28		Loss of glycosylation at P21 (P = 0.0061)
MVP		0.35
MPC		0.88
ClinPred		0.29	T
GERP RS		1.7
PromoterAI		-0.038	Neutral
Varity_R		0.086
gMVP		0.060
Mutation Taster		=297/3	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

hg19: chr1-1407326;