rs200927073

Variant names:

• chr9-7799673-G-A
• NM_033428.3:c.62C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-7799673-G-A
• chr9-7799673-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.62C>T​(p.Ala21Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000757 in 1,454,028 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. A21G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000076 (0 hom.)
• Consequence: DMAC1 NM_033428.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.519

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=0.10313445).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DMAC1	NM_033428.3	c.62C>T	p.Ala21Val	missense_variant	Exon 1 of 2	ENST00000358227.5	NP_219500.1
DMAC1	NM_001318059.2	c.62C>T	p.Ala21Val	missense_variant	Exon 1 of 2		NP_001304988.1
DMAC1	NM_001318058.2	c.62C>T	p.Ala21Val	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.62C>T	p.Ala21Val	missense_variant	Exon 1 of 2	1	NM_033428.3	ENSP00000350961.4
DMAC1	ENST00000469050.1	n.165-1036C>T		intron_variant	Intron 2 of 2	3
DMAC1	ENST00000484082.1	n.108+368C>T		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000757 AC: 11 AN: 1454028 Hom.: 0 Cov.: 34 AF XY: 0.0000111 AC XY: 8 AN XY: 723004

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: 0.00000901

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	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	12
DANN	Uncertain	1.0
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.077
Sift	Benign	0.035	D
Sift4G	Uncertain	0.033	D
Polyphen		0.39	B
Vest4		0.15
MutPred		0.20		Gain of sheet (P = 0.0125);
MVP		0.35
MPC		0.30
ClinPred		0.35	T
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
gMVP		0.31

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: chr9-7799673;