Variant chr9-7799610-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_033428.3(DMAC1):c.125G>A(p.Arg42His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000329 in 1,613,370 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

DMAC1
NM_033428.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.176

Variant links:

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]

DMAC1 links:

DMAC1 (HGNC:):

DMAC1 links:

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ACMG classification

Classification made for transcript

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=0.06974992).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
DMAC1	NM_033428.3 linkuse as main transcript	c.125G>A	p.Arg42His	missense_variant	1/2	ENST00000358227.5	NP_219500.1
DMAC1	NM_001318059.2 linkuse as main transcript	c.125G>A	p.Arg42His	missense_variant	1/2		NP_001304988.1
DMAC1	NM_001318058.2 linkuse as main transcript	c.125G>A	p.Arg42His	missense_variant	1/2		NP_001304987.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DMAC1	ENST00000358227.5 linkuse as main transcript	c.125G>A	p.Arg42His	missense_variant	1/2	1	NM_033428.3	ENSP00000350961.4	Q96GE9-2
DMAC1	ENST00000469050.1 linkuse as main transcript	n.165-973G>A		intron_variant		3
DMAC1	ENST00000484082.1 linkuse as main transcript	n.108+431G>A		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

152076

Hom.:

Cov.:

show subpopulations

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:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000599

AC:

AN:

250574

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135598

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000124

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000322

AC:

AN:

1461294

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

726928

show subpopulations

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000342

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.0000395

AC:

AN:

152076

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000330

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.000115

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 16, 2021

The c.125G>A (p.R42H) alteration is located in exon 1 (coding exon 1) of the TMEM261 gene. This alteration results from a G to A substitution at nucleotide position 125, causing the arginine (R) at amino acid position 42 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.67

CADD

Benign

5.2

DANN

Benign

0.97

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.38

M_CAP

Benign

0.010

MetaRNN

Benign

0.070

MetaSVM

Benign

-0.98

PROVEAN

Benign

-0.44

REVEL

Benign

0.037

Sift

Benign

0.25

Sift4G

Benign

0.23

Polyphen

0.90

Vest4

0.093

MVP

0.14

MPC

0.23

ClinPred

0.073

GERP RS

-3.0

gMVP

0.48

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over