dbSNP rs367919742: MGARP:p.Asp121Tyr (chr4-139266961-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032623.4(MGARP):c.361G>T(p.Asp121Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. D121N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MGARP
NM_032623.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.980

Publications

0 publications found

Variant links:

Genes affected

MGARP (HGNC:29969): (mitochondria localized glutamic acid rich protein) Predicted to be involved in several processes, including axonal transport; cellular response to hormone stimulus; and protein targeting to mitochondrion. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

MGARP links:

NDUFC1 (HGNC:7705): (NADH:ubiquinone oxidoreductase subunit C1) The encoded protein is a subunit of the NADH:ubiquinone oxidoreductase (complex I), the first enzyme complex in the electron transport chain located in the inner mitochondrial membrane. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

NDUFC1 links:

ENSG00000288785 (HGNC:58885):

ENSG00000288785 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08750352).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032623.4. 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
	MGARP	NM_032623.4	MANE Select	c.361G>T	p.Asp121Tyr	missense	Exon 4 of 4	NP_116012.2	Q8TDB4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MGARP	ENST00000398955.2	TSL:1 MANE Select	c.361G>T	p.Asp121Tyr	missense	Exon 4 of 4	ENSP00000381928.1	Q8TDB4
MGARP	ENST00000962439.1		c.281-61G>T		intron	N/A	ENSP00000632498.1
NDUFC1	ENST00000503997.5	TSL:3	n.*299G>T		non_coding_transcript_exon	Exon 6 of 6	ENSP00000425882.1	O43677

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461884

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1112006

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.59

DEOGEN2

Benign

0.038

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.080

LIST_S2

Benign

0.36

M_CAP

Benign

0.016

MetaRNN

Benign

0.088

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.4

PhyloP100

-0.98

PrimateAI

Benign

0.27

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.052

Sift

Benign

1.0

Sift4G

Uncertain

0.034

Polyphen

0.92

Vest4

0.16

MutPred

0.31

Gain of phosphorylation at D121 (P = 0.0073)

MVP

0.088

MPC

0.53

ClinPred

0.59

GERP RS

2.2

Varity_R

0.050

gMVP

0.092

Mutation Taster

=95/5

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over