dbSNP rs201338144: COXFA4L2:p.Arg61Leu (chr12-57235774-C-A) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001394961.1(COXFA4L2):c.182G>T(p.Arg61Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000119 in 1,426,674 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R61C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

COXFA4L2
NM_001394961.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.83

Publications

3 publications found

Variant links:

Genes affected

COXFA4L2 (HGNC:29836): (NDUFA4 mitochondrial complex associated like 2) Predicted to be integral component of membrane. Predicted to be part of mitochondrial respiratory chain complex IV. [provided by Alliance of Genome Resources, Apr 2022]

COXFA4L2 links:

ENSG00000295078 (HGNC:):

ENSG00000295078 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3190074).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394961.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COXFA4L2	NM_001394961.1	MANE Select	c.182G>T	p.Arg61Leu	missense	Exon 3 of 4	NP_001381890.1	Q9NRX3
COXFA4L2	NM_001394960.1		c.182G>T	p.Arg61Leu	missense	Exon 4 of 5	NP_001381889.1	Q9NRX3
COXFA4L2	NM_020142.4		c.182G>T	p.Arg61Leu	missense	Exon 4 of 5	NP_064527.1	Q9NRX3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NDUFA4L2	ENST00000554503.6	TSL:1 MANE Select	c.182G>T	p.Arg61Leu	missense	Exon 3 of 4	ENSP00000450664.1	Q9NRX3
NDUFA4L2	ENST00000393825.5	TSL:1	c.182G>T	p.Arg61Leu	missense	Exon 4 of 5	ENSP00000377411.1	Q9NRX3
NDUFA4L2	ENST00000909958.1		c.338G>T	p.Arg113Leu	missense	Exon 4 of 5	ENSP00000580017.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000881

AC:

AN:

226994

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.0000119

AC:

AN:

1426674

Hom.:

Cov.:

AF XY:

0.00000993

AC XY:

AN XY:

704962

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32598

American (AMR)

AF:

0.00

AC:

AN:

42090

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24128

East Asian (EAS)

AF:

0.00

AC:

AN:

39178

South Asian (SAS)

AF:

0.000184

AC:

AN:

81588

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52262

Middle Eastern (MID)

AF:

0.000179

AC:

AN:

5582

European-Non Finnish (NFE)

AF:

9.17e-7

AC:

AN:

1090486

Other (OTH)

AF:

0.00

AC:

AN:

58762

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.31

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.22

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.82

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.32

MetaSVM

Benign

-0.47

PhyloP100

1.8

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-3.9

REVEL

Benign

0.25

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.042

Polyphen

0.98

Vest4

0.51

MutPred

0.29

Loss of disorder (P = 0.046)

MVP

0.78

MPC

0.052

ClinPred

0.83

GERP RS

1.6

Varity_R

0.32

gMVP

0.30

Mutation Taster

=91/9

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over