rs753223143

Variant names:

• chr12-57235798-T-C
• NM_001394961.1:c.158A>G

Your query was ambiguous. Multiple possible variants found:

• chr12-57235798-T-C
• chr12-57235798-T-G

Variant summary

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

The NM_001394961.1(NDUFA4L2):​c.158A>G​(p.Lys53Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000215 in 1,396,616 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: NDUFA4L2 NM_001394961.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.84

Genes affected

NDUFA4L2 (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]

ACMG classification

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
NDUFA4L2	NM_001394961.1	c.158A>G	p.Lys53Arg	missense_variant	Exon 3 of 4	ENST00000554503.6	NP_001381890.1
NDUFA4L2	NM_001394960.1	c.158A>G	p.Lys53Arg	missense_variant	Exon 4 of 5		NP_001381889.1
NDUFA4L2	NM_020142.4	c.158A>G	p.Lys53Arg	missense_variant	Exon 4 of 5		NP_064527.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFA4L2	ENST00000554503.6	c.158A>G	p.Lys53Arg	missense_variant	Exon 3 of 4	1	NM_001394961.1	ENSP00000450664.1
NDUFA4L2	ENST00000393825.5	c.158A>G	p.Lys53Arg	missense_variant	Exon 4 of 5	1		ENSP00000377411.1
NDUFA4L2	ENST00000556732.1	c.158A>G	p.Lys53Arg	missense_variant	Exon 3 of 3	3		ENSP00000452193.1
NDUFA4L2	ENST00000555173.1	n.442A>G		non_coding_transcript_exon_variant	Exon 3 of 4	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000215 AC: 3 AN: 1396616 Hom.: 0 Cov.: 31 AF XY: 0.00000291 AC XY: 2 AN XY: 686594

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000279

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.0023	T
BayesDel_noAF	Benign	-0.24
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	T;T;T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.85	.;D;D
M_CAP	Pathogenic	0.29	D
MetaRNN	Uncertain	0.43	T;T;T
MetaSVM	Uncertain	-0.17	T
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-2.5	N;N;N
REVEL	Uncertain	0.44
Sift	Uncertain	0.0050	D;D;T
Sift4G	Uncertain	0.040	D;D;D
Polyphen		0.99	D;D;.
Vest4		0.45
MutPred		0.46		Loss of catalytic residue at K53 (P = 0.0045);Loss of catalytic residue at K53 (P = 0.0045);Loss of catalytic residue at K53 (P = 0.0045);
MVP		0.87
MPC		0.086
ClinPred		0.98	D
GERP RS		4.4
Varity_R		0.29
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-57629581;