rs183380179

Variant names:

• chr12-57237060-C-A
• rs183380179
• NM_001394961.1:c.26G>T

Your query was ambiguous. Multiple possible variants found:

• chr12-57237060-C-A
• chr12-57237060-C-G
• chr12-57237060-C-T

Variant summary

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

The NM_001394961.1(COXFA4L2):​c.26G>T​(p.Arg9Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R9H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: COXFA4L2 NM_001394961.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.697
• Publications: 2 publications found

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]

ENSG00000295078 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COXFA4L2	NM_001394961.1	MANE Select	c.26G>T	p.Arg9Leu	missense	Exon 1 of 4	NP_001381890.1	Q9NRX3
	COXFA4L2	NM_001394960.1		c.26G>T	p.Arg9Leu	missense	Exon 2 of 5	NP_001381889.1	Q9NRX3
	COXFA4L2	NM_020142.4		c.26G>T	p.Arg9Leu	missense	Exon 2 of 5	NP_064527.1	Q9NRX3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFA4L2	ENST00000554503.6	TSL:1 MANE Select	c.26G>T	p.Arg9Leu	missense	Exon 1 of 4	ENSP00000450664.1	Q9NRX3
	NDUFA4L2	ENST00000393825.5	TSL:1	c.26G>T	p.Arg9Leu	missense	Exon 2 of 5	ENSP00000377411.1	Q9NRX3
	NDUFA4L2	ENST00000909958.1		c.26G>T	p.Arg9Leu	missense	Exon 1 of 5	ENSP00000580017.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461892 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727248

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000193 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.062	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.79	T
M_CAP	Uncertain	0.097	D
MetaRNN	Uncertain	0.50	D
MetaSVM	Benign	-0.76	T
PhyloP100		0.70
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	0.29	N
REVEL	Uncertain	0.49
Sift	Benign	0.35	T
Sift4G	Benign	0.32	T
Polyphen		0.18	B
Vest4		0.48
MVP		0.74
MPC		0.028
ClinPred		0.91	D
GERP RS		3.7
PromoterAI		-0.10	Neutral
Varity_R		0.12
gMVP		0.39
Mutation Taster		=97/3	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

dbSNP: rs183380179; hg19: chr12-57630843;