19-41431190-G-A

Variant names:

• chr19-41431190-G-A
• rs17318596
• NM_018035.3:c.*1041C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018035.3(DMAC2):​c.*1041C>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 518,682 control chromosomes in the GnomAD database, including 38,178 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.33 (9188 hom., cov: 32)
  • Exomes 𝑓: 0.39 (28990 hom.)
• Consequence: DMAC2 NM_018035.3 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.48
• Publications: 76 publications found

Genes affected

DMAC2 (HGNC:25496): (distal membrane arm assembly component 2) Involved in mitochondrial respiratory chain complex I assembly. Colocalizes with mitochondrial respiratory chain complex I. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.011).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018035.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMAC2	NM_018035.3	MANE Select	c.*1041C>T		downstream_gene	N/A	NP_060505.2
	DMAC2	NM_001167867.2		c.*1041C>T		downstream_gene	N/A	NP_001161339.1
	DMAC2	NM_001320840.2		c.*1041C>T		downstream_gene	N/A	NP_001307769.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMAC2	ENST00000221943.14	TSL:2 MANE Select	c.*1041C>T		downstream_gene	N/A	ENSP00000221943.8
	DMAC2	ENST00000438807.7	TSL:1	c.*1094C>T		downstream_gene	N/A	ENSP00000397413.3
	DMAC2	ENST00000592922.6	TSL:2	c.*1041C>T		downstream_gene	N/A	ENSP00000467205.1

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50488 AN: 151862 Hom.: 9174 Cov.: 32

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.561

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.347

GnomAD2 exomes AF: 0.398 AC: 91165 AN: 229234 AF XY: 0.396

Gnomad AFR exome AF: 0.191

Gnomad AMR exome AF: 0.507

Gnomad ASJ exome AF: 0.374

Gnomad EAS exome AF: 0.565

Gnomad FIN exome AF: 0.341

Gnomad NFE exome AF: 0.370

Gnomad OTH exome AF: 0.377

GnomAD4 exome AF: 0.391 AC: 143302 AN: 366702 Hom.: 28990 Cov.: 0 AF XY: 0.392 AC XY: 82463 AN XY: 210264

African (AFR) AF: 0.196 AC: 2056 AN: 10510

American (AMR) AF: 0.506 AC: 18356 AN: 36302

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 4396 AN: 11744

East Asian (EAS) AF: 0.559 AC: 7357 AN: 13172

South Asian (SAS) AF: 0.409 AC: 27287 AN: 66766

European-Finnish (FIN) AF: 0.340 AC: 5745 AN: 16910

Middle Eastern (MID) AF: 0.355 AC: 1012 AN: 2852

European-Non Finnish (NFE) AF: 0.370 AC: 70971 AN: 191836

Other (OTH) AF: 0.369 AC: 6122 AN: 16610

GnomAD4 genome AF: 0.333 AC: 50537 AN: 151980 Hom.: 9188 Cov.: 32 AF XY: 0.336 AC XY: 24959 AN XY: 74270

African (AFR) AF: 0.197 AC: 8164 AN: 41460

American (AMR) AF: 0.423 AC: 6449 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 1288 AN: 3470

East Asian (EAS) AF: 0.560 AC: 2894 AN: 5168

South Asian (SAS) AF: 0.404 AC: 1944 AN: 4814

European-Finnish (FIN) AF: 0.330 AC: 3484 AN: 10548

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.372 AC: 25288 AN: 67960

Other (OTH) AF: 0.350 AC: 738 AN: 2110

Alfa AF: 0.363 Hom.: 39419

Bravo AF: 0.334

Asia WGS AF: 0.465 AC: 1619 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Pathogenic	0.15
CADD	Benign	0.045
DANN	Benign	0.90
PhyloP100		-2.5

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17318596; hg19: chr19-41937095; COSMIC: COSV55729421;