chr19-41433321-C-T

Variant names:

• chr19-41433321-C-T
• rs367830809
• NM_018035.3:c.547G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_018035.3(DMAC2):​c.547G>A​(p.Gly183Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000235 in 1,611,470 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00021 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00024 (0 hom.)
• Consequence: DMAC2 NM_018035.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.28
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.12565267).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMAC2	NM_018035.3	MANE Select	c.547G>A	p.Gly183Ser	missense	Exon 5 of 6	NP_060505.2	Q9NW81-1
	DMAC2	NM_001167867.2		c.565G>A	p.Gly189Ser	missense	Exon 5 of 6	NP_001161339.1	Q9NW81-4
	DMAC2	NM_001320840.2		c.484G>A	p.Gly162Ser	missense	Exon 4 of 5	NP_001307769.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMAC2	ENST00000221943.14	TSL:2 MANE Select	c.547G>A	p.Gly183Ser	missense	Exon 5 of 6	ENSP00000221943.8	Q9NW81-1
	DMAC2	ENST00000438807.7	TSL:1	c.352+216G>A		intron	N/A	ENSP00000397413.3	Q9NW81-2
	DMAC2	ENST00000417807.7	TSL:2	c.565G>A	p.Gly189Ser	missense	Exon 5 of 6	ENSP00000403910.2	Q9NW81-4

Frequencies

GnomAD3 genomes AF: 0.000204 AC: 31 AN: 152160 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000323 AC: 80 AN: 247648 AF XY: 0.000335

Gnomad AFR exome AF: 0.0000627

Gnomad AMR exome AF: 0.0000869

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000864

Gnomad NFE exome AF: 0.000498

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000238 AC: 347 AN: 1459192 Hom.: 0 Cov.: 30 AF XY: 0.000271 AC XY: 197 AN XY: 726062

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.0000895 AC: 4 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000209 AC: 18 AN: 86234

European-Finnish (FIN) AF: 0.000566 AC: 29 AN: 51270

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5512

European-Non Finnish (NFE) AF: 0.000256 AC: 285 AN: 1111858

Other (OTH) AF: 0.000182 AC: 11 AN: 60332

GnomAD4 genome AF: 0.000210 AC: 32 AN: 152278 Hom.: 0 Cov.: 31 AF XY: 0.000215 AC XY: 16 AN XY: 74460

African (AFR) AF: 0.0000241 AC: 1 AN: 41548

American (AMR) AF: 0.00 AC: 0 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4830

European-Finnish (FIN) AF: 0.000565 AC: 6 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000338 AC: 23 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.000244 Hom.: 0

Bravo AF: 0.000162

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000362 AC: 44

EpiCase AF: 0.000327

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.46
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.061	T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.25	N
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.75	T
PhyloP100		1.3
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.14
Sift	Benign	0.050	D
Sift4G	Uncertain	0.027	D
Polyphen		1.0	D
Vest4		0.50
MVP		0.69
MPC		0.69
ClinPred		0.061	T
GERP RS		3.4
Varity_R		0.092
gMVP		0.55
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs367830809; hg19: chr19-41939226;