rs1225143900

Variant names:

• chr9-7799664-G-A
• NM_033428.3:c.71C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-7799664-G-A
• chr9-7799664-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033428.3(DMAC1):​c.71C>T​(p.Ala24Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,936 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/17 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. A24G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DMAC1 NM_033428.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31

Genes affected

DMAC1 (HGNC:30536): (distal membrane arm assembly component 1) Involved in mitochondrial respiratory chain complex I assembly. Located in mitochondrial inner membrane. Colocalizes with mitochondrial respiratory chain complex I. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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=0.16902804).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DMAC1	NM_033428.3	c.71C>T	p.Ala24Val	missense_variant	Exon 1 of 2	ENST00000358227.5	NP_219500.1
DMAC1	NM_001318059.2	c.71C>T	p.Ala24Val	missense_variant	Exon 1 of 2		NP_001304988.1
DMAC1	NM_001318058.2	c.71C>T	p.Ala24Val	missense_variant	Exon 1 of 2		NP_001304987.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DMAC1	ENST00000358227.5	c.71C>T	p.Ala24Val	missense_variant	Exon 1 of 2	1	NM_033428.3	ENSP00000350961.4
DMAC1	ENST00000469050.1	n.165-1027C>T		intron_variant	Intron 2 of 2	3
DMAC1	ENST00000484082.1	n.108+377C>T		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455936 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 724012

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: 0.0000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	18
DANN	Uncertain	1.0
Eigen	Benign	-0.068
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.89	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.13
Sift	Benign	0.050	D
Sift4G	Uncertain	0.029	D
Polyphen		0.99	D
Vest4		0.16
MutPred		0.12		Loss of relative solvent accessibility (P = 0.0404);
MVP		0.45
MPC		0.19
ClinPred		0.39	T
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.58

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: chr9-7799664;