Genetic Variant MNS1:p.Arg425His (chr15-56431494-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_018365.4(MNS1):c.1274G>A(p.Arg425His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00151 in 1,613,420 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0013 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 5 hom. )

Consequence

MNS1
NM_018365.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.434

Publications

5 publications found

Variant links:

Genes affected

MNS1 (HGNC:29636): (meiosis specific nuclear structural 1) This gene encodes a protein highly similar to the mouse meiosis-specific nuclear structural 1 protein. The mouse protein was shown to be expressed at the pachytene stage during spermatogenesis and may function as a nuclear skeletal protein to regulate nuclear morphology during meiosis. [provided by RefSeq, Oct 2008]

MNS1 links:

TEX9 (HGNC:29585): (testis expressed 9)

TEX9 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0076506734).

BP6

Variant 15-56431494-C-T is Benign according to our data. Variant chr15-56431494-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3046071.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00134 (204/152226) while in subpopulation SAS AF = 0.00249 (12/4818). AF 95% confidence interval is 0.00144. There are 2 homozygotes in GnomAd4. There are 97 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018365.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MNS1	NM_018365.4	MANE Select	c.1274G>A	p.Arg425His	missense	Exon 9 of 10	NP_060835.1	Q8NEH6
TEX9	NM_198524.3		c.*29+3021C>T		intron	N/A	NP_940926.1	A0A0S2Z669
TEX9	NM_001286449.2		c.*29+3021C>T		intron	N/A	NP_001273378.1	Q8N6V9-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MNS1	ENST00000260453.4	TSL:1 MANE Select	c.1274G>A	p.Arg425His	missense	Exon 9 of 10	ENSP00000260453.3	Q8NEH6
TEX9	ENST00000352903.6	TSL:1	c.*29+3021C>T		intron	N/A	ENSP00000342169.2	Q8N6V9-1
MNS1	ENST00000957022.1		c.1307G>A	p.Arg436His	missense	Exon 9 of 10	ENSP00000627081.1

Frequencies

GnomAD3 genomes

AF:

0.00130

AC:

197

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00111

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000852

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00249

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00159

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.00140

AC:

352

AN:

250610

AF XY:

0.00157

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.000756

Gnomad ASJ exome

AF:

0.00268

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000925

Gnomad NFE exome

AF:

0.00129

Gnomad OTH exome

AF:

0.00148

GnomAD4 exome

AF:

0.00153

AC:

2235

AN:

1461194

Hom.:

Cov.:

AF XY:

0.00165

AC XY:

1197

AN XY:

726904

show subpopulations

African (AFR)

AF:

0.00102

AC:

AN:

33452

American (AMR)

AF:

0.000897

AC:

AN:

44616

Ashkenazi Jewish (ASJ)

AF:

0.00256

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39674

South Asian (SAS)

AF:

0.00356

AC:

307

AN:

86176

European-Finnish (FIN)

AF:

0.0000750

AC:

AN:

53366

Middle Eastern (MID)

AF:

0.00249

AC:

AN:

5614

European-Non Finnish (NFE)

AF:

0.00149

AC:

1662

AN:

1111828

Other (OTH)

AF:

0.00177

AC:

107

AN:

60344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

108

217

325

434

542

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

136

204

272

340

<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:

0.00134

AC:

204

AN:

152226

Hom.:

Cov.:

AF XY:

0.00130

AC XY:

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.00128

AC:

AN:

41540

American (AMR)

AF:

0.000851

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00403

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00249

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.0000944

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00159

AC:

108

AN:

68022

Other (OTH)

AF:

0.00142

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

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:

0.00144

Hom.:

Bravo

AF:

0.00133

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000912

AC:

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.00147

AC:

179

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.00158

EpiControl

AF:

0.00166

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

MNS1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.064

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.48

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.80

M_CAP

Benign

0.0060

MetaRNN

Benign

0.0077

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.9

PhyloP100

0.43

PrimateAI

Benign

0.21

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.12

Sift

Uncertain

0.020

Sift4G

Uncertain

0.052

Polyphen

0.99

Vest4

0.16

MVP

0.088

MPC

0.052

ClinPred

0.032

GERP RS

0.97

Varity_R

0.11

gMVP

0.33

Mutation Taster

=96/4

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over