Genetic Variant MINAR2:p.Arg138Gly (chr5-129764902-C-G) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP2

The NM_001257308.2(MINAR2):c.412C>G(p.Arg138Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000171 in 1,171,800 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R138W) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000017 ( 0 hom. )

Consequence

MINAR2
NM_001257308.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.75

Publications

0 publications found

Variant links:

Genes affected

MINAR2 (HGNC:33914): (membrane integral NOTCH2 associated receptor 2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

MINAR2 Gene-Disease associations (from GenCC):

hearing loss, autosomal recessive 120
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

MINAR2 links:

CHSY3-AS1 (HGNC:58253):

CHSY3-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 1 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 0.67277 (below the threshold of 3.09). Trascript score misZ: -1.285 (below the threshold of 3.09). GenCC associations: The gene is linked to hearing loss, autosomal recessive 120.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001257308.2. 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
	MINAR2	NM_001257308.2	MANE Select	c.412C>G	p.Arg138Gly	missense	Exon 3 of 3	NP_001244237.1	P59773

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MINAR2	ENST00000564719.2	TSL:5 MANE Select	c.412C>G	p.Arg138Gly	missense	Exon 3 of 3	ENSP00000454268.1	P59773
CHSY3-AS1	ENST00000503616.5	TSL:3	n.122-2233G>C		intron	N/A
CHSY3-AS1	ENST00000515569.1	TSL:2	n.286-2233G>C		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000171

AC:

AN:

1171800

Hom.:

Cov.:

AF XY:

0.00000178

AC XY:

AN XY:

562670

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25464

American (AMR)

AF:

0.00

AC:

AN:

13990

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16700

East Asian (EAS)

AF:

0.00

AC:

AN:

30724

South Asian (SAS)

AF:

0.00

AC:

AN:

37984

European-Finnish (FIN)

AF:

0.00

AC:

AN:

26228

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4850

European-Non Finnish (NFE)

AF:

0.00000207

AC:

AN:

967704

Other (OTH)

AF:

0.00

AC:

AN:

48156

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

0.33

BayesDel_addAF

Uncertain

0.045

BayesDel_noAF

Benign

-0.17

CADD

Benign

(source)

DANN

Uncertain

1.0

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.84

M_CAP

Benign

0.014

MetaRNN

Benign

0.42

PhyloP100

1.8

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-2.0

Sift

Uncertain

0.019

Sift4G

Benign

0.10

Vest4

0.41

MVP

0.77

GERP RS

4.8

gMVP

0.25

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.24

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.24

Position offset: -18

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

Publications

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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