Genetic Variant MINAR2:p.Arg138Trp (chr5-129764902-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 1P and 5B. PP2BP4_StrongBP6

The NM_001257308.2(MINAR2):c.412C>T(p.Arg138Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000258 in 1,323,974 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

MINAR2
NM_001257308.2 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.75

Publications

3 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: Likely_benign. The variant received -4 ACMG points.

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.

BP4

Computational evidence support a benign effect (MetaRNN=0.014112711).

BP6

Variant 5-129764902-C-T is Benign according to our data. Variant chr5-129764902-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3355390.Status of the report is no_assertion_criteria_provided, 0 stars.

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>T	p.Arg138Trp	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>T	p.Arg138Trp	missense	Exon 3 of 3	ENSP00000454268.1	P59773
CHSY3-AS1	ENST00000503616.5	TSL:3	n.122-2233G>A		intron	N/A
CHSY3-AS1	ENST00000515569.1	TSL:2	n.286-2233G>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00128

AC:

195

AN:

152056

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00445

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.000959

GnomAD2 exomes

AF:

0.000262

AC:

AN:

38108

AF XY:

0.000298

show subpopulations

Gnomad AFR exome

AF:

0.00328

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000846

GnomAD4 exome

AF:

0.000123

AC:

144

AN:

1171800

Hom.:

Cov.:

AF XY:

0.0000995

AC XY:

AN XY:

562670

show subpopulations

African (AFR)

AF:

0.00334

AC:

AN:

25464

American (AMR)

AF:

0.000286

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:

0.0000263

AC:

AN:

37984

European-Finnish (FIN)

AF:

0.00

AC:

AN:

26228

Middle Eastern (MID)

AF:

0.000206

AC:

AN:

4850

European-Non Finnish (NFE)

AF:

0.0000413

AC:

AN:

967704

Other (OTH)

AF:

0.000270

AC:

AN:

48156

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

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

AF:

0.00129

AC:

197

AN:

152174

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

102

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.00446

AC:

185

AN:

41512

American (AMR)

AF:

0.000327

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10580

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68014

Other (OTH)

AF:

0.000949

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000695

Hom.:

Bravo

AF:

0.00133

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ExAC

AF:

0.000222

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

MINAR2-related condition (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.23

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.017

MetaRNN

Benign

0.014

PhyloP100

1.8

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-3.4

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0090

Vest4

0.42

MVP

0.76

GERP RS

4.8

gMVP

0.31

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

Details are displayed if max score is > 0.2

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over