4-673942-G-A

Position:

chr4-673942-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000304312.5(ATP5ME):c.61C>T(p.Leu21Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000408 in 1,546,004 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

ATP5ME
ENST00000304312.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.391

Variant links:

Genes affected

ATP5ME (HGNC:846): (ATP synthase membrane subunit e) Mitochondrial ATP synthase catalyzes ATP synthesis, utilizing an electrochemical gradient of protons across the inner membrane during oxidative phosphorylation. It is composed of two linked multi-subunit complexes: the soluble catalytic core, F1, and the membrane-spanning component, Fo, which comprises the proton channel. The F1 complex consists of 5 different subunits (alpha, beta, gamma, delta, and epsilon) assembled in a ratio of 3 alpha, 3 beta, and a single representative of the other 3. The Fo seems to have nine subunits (a, b, c, d, e, f, g, F6 and 8). This gene encodes the e subunit of the Fo complex. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Jun 2010]

ATP5ME links:

MYL5 (HGNC:7586): (myosin light chain 5) This gene encodes one of the myosin light chains, a component of the hexameric ATPase cellular motor protein myosin. Myosin is composed of two heavy chains, two nonphosphorylatable alkali light chains, and two phosphorylatable regulatory light chains. This gene product, one of the regulatory light chains, is expressed in fetal muscle and in adult retina, cerebellum, and basal ganglia. [provided by RefSeq, Jul 2008]

MYL5 links:

ATP5ME (HGNC:):

ATP5ME links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.082295746).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP5ME	NM_007100.4 linkuse as main transcript	c.61C>T	p.Leu21Phe	missense_variant	2/4	ENST00000304312.5	NP_009031.1	P56385
ATP5ME	NR_033743.2 linkuse as main transcript	n.65+270C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP5ME	ENST00000304312.5 linkuse as main transcript	c.61C>T	p.Leu21Phe	missense_variant	2/4	1	NM_007100.4	ENSP00000306003.4		P56385

Frequencies

GnomAD3 genomes

AF:

0.000223

AC:

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000797

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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

GnomAD3 exomes

AF:

0.0000421

AC:

AN:

142546

Hom.:

AF XY:

0.0000649

AC XY:

AN XY:

77022

show subpopulations

Gnomad AFR exome

AF:

0.000705

Gnomad AMR exome

AF:

0.0000407

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000215

AC:

AN:

1393758

Hom.:

Cov.:

AF XY:

0.0000233

AC XY:

AN XY:

687622

show subpopulations

Gnomad4 AFR exome

AF:

0.000855

Gnomad4 AMR exome

AF:

0.0000280

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000173

GnomAD4 genome

AF:

0.000217

AC:

AN:

152246

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.000771

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000212

ExAC

AF:

0.0000420

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 27, 2022

The c.61C>T (p.L21F) alteration is located in exon 2 (coding exon 2) of the ATP5I gene. This alteration results from a C to T substitution at nucleotide position 61, causing the leucine (L) at amino acid position 21 to be replaced by a phenylalanine (F). 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

0.15

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.42

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.17

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.060

MetaRNN

Benign

0.082

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.059

Sift

Uncertain

0.0070

Sift4G

Benign

0.085

Polyphen

0.78

Vest4

0.40

MVP

0.23

MPC

0.11

ClinPred

0.16

GERP RS

1.1

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.0

Varity_R

0.15

gMVP

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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