Genetic Variant ATP5IF1:p.Gly16Val (chr1-28236230-G-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016311.5(ATP5IF1):c.47G>T(p.Gly16Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000806 in 1,613,810 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000082 ( 0 hom. )

Consequence

ATP5IF1
NM_016311.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.78

Variant links:

Genes affected

ATP5IF1 (HGNC:871): (ATP synthase inhibitory factor subunit 1) Enables several functions, including ATPase binding activity; angiostatin binding activity; and mitochondrial proton-transporting ATP synthase complex binding activity. Involved in several processes, including mitochondrial depolarization; negative regulation of ATPase activity; and regulation of protein targeting to mitochondrion. Located in cell surface and mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ATP5IF1 links:

ENSG00000290123 (HGNC:):

ENSG00000290123 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP5IF1	NM_016311.5 link	c.47G>T	p.Gly16Val	missense_variant	Exon 1 of 3	ENST00000335514.10	NP_057395.1	Q9UII2-1
ATP5IF1	NM_178190.3 link	c.47G>T	p.Gly16Val	missense_variant	Exon 1 of 3		NP_835497.1	Q9UII2-2
ATP5IF1	NM_178191.3 link	c.47G>T	p.Gly16Val	missense_variant	Exon 1 of 2		NP_835498.1	Q9UII2-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP5IF1	ENST00000335514.10 link	c.47G>T	p.Gly16Val	missense_variant	Exon 1 of 3	1	NM_016311.5	ENSP00000335203.5		Q9UII2-1

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152262

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000878

AC:

AN:

250706

Hom.:

AF XY:

0.0000811

AC XY:

AN XY:

135716

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000465

Gnomad NFE exome

AF:

0.000124

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000821

AC:

120

AN:

1461548

Hom.:

Cov.:

AF XY:

0.0000798

AC XY:

AN XY:

727130

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.0000980

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152262

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000135

Hom.:

Bravo

AF:

0.000110

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000115

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 27, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.47G>T (p.G16V) alteration is located in exon 1 (coding exon 1) of the ATPIF1 gene. This alteration results from a G to T substitution at nucleotide position 47, causing the glycine (G) at amino acid position 16 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.053

BayesDel_noAF

Uncertain

-0.030

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.10

.;T;T;.

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Pathogenic

0.99

M_CAP

Benign

0.032

MetaRNN

Uncertain

0.58

D;D;D;D

MetaSVM

Benign

-0.46

MutationAssessor

Uncertain

2.4

M;M;.;M

PrimateAI

Benign

0.44

PROVEAN

Pathogenic

-4.7

D;D;D;D

REVEL

Benign

0.19

Sift

Uncertain

0.0050

D;D;D;D

Sift4G

Uncertain

0.018

D;D;D;D

Polyphen

1.0

D;D;.;.

Vest4

0.60

MVP

0.60

MPC

1.0

ClinPred

0.90

GERP RS

5.1

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Varity_R

0.37

gMVP

0.14

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over