14-50321516-A-G

Variant names:

• chr14-50321516-A-G
• rs1279572411
• NM_001382507.1:c.29A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001382507.1(DMAC2L):​c.29A>G​(p.Gln10Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. 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. Q10L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DMAC2L NM_001382507.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.440
• Publications: 0 publications found

Genes affected

DMAC2L (HGNC:18799): (distal membrane arm assembly component 2 like) This gene encodes a subunit of mitochondrial ATP synthase. Mitochondrial ATP synthase catalyzes ATP synthesis, utilizing an electrochemical gradient of protons across the inner membrane during oxidative phosphorylation. ATP synthase is composed of two linked multi-subunit complexes: the soluble catalytic core, F1, and the membrane-spanning component, Fo, comprising the proton channel. This gene encodes the subunit s, also known as factor B, of the proton channel. This subunit is necessary for the energy transduction activity of the ATP synthase complexes. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04542467).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382507.1. 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
	DMAC2L	NM_001382507.1	MANE Select	c.29A>G	p.Gln10Arg	missense	Exon 3 of 6	NP_001369436.1	Q99766-1
	DMAC2L	NM_001003803.3		c.29A>G	p.Gln10Arg	missense	Exon 2 of 5	NP_001003803.2	Q99766-1
	DMAC2L	NM_001370605.1		c.29A>G	p.Gln10Arg	missense	Exon 3 of 6	NP_001357534.1	Q99766-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMAC2L	ENST00000557421.7	TSL:5 MANE Select	c.29A>G	p.Gln10Arg	missense	Exon 3 of 6	ENSP00000506374.1	Q99766-1
	DMAC2L	ENST00000311459.12	TSL:1	c.29A>G	p.Gln10Arg	missense	Exon 2 of 5	ENSP00000308334.8	Q99766-1
	DMAC2L	ENST00000554204.7	TSL:1	c.29A>G	p.Gln10Arg	missense	Exon 2 of 5	ENSP00000451583.3	Q99766-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	10
DANN	Benign	0.80
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.045	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.44
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.030	N
REVEL	Benign	0.0080
Sift	Benign	0.33	T
Sift4G	Benign	0.67	T
Vest4		0.063
MutPred		0.37		Gain of catalytic residue at Q25 (P = 0.0179)
MVP		0.31
MPC		0.20
ClinPred		0.044	T
GERP RS		0.19
PromoterAI		0.018	Neutral
gMVP		0.14
Mutation Taster		=94/6	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: rs1279572411; hg19: chr14-50788234;