15-56431494-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -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. 12/21 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

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 made for transcript

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MNS1	NM_018365.4 link	c.1274G>A	p.Arg425His	missense_variant	Exon 9 of 10	ENST00000260453.4	NP_060835.1	Q8NEH6B3KQ70

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MNS1	ENST00000260453.4 link	c.1274G>A	p.Arg425His	missense_variant	Exon 9 of 10	1	NM_018365.4	ENSP00000260453.3	Q8NEH6
TEX9	ENST00000352903.6 link	c.*29+3021C>T		intron_variant	Intron 12 of 12	1		ENSP00000342169.2	Q8N6V9-1
MNS1	ENST00000566386.1 link	n.75G>A		non_coding_transcript_exon_variant	Exon 2 of 4	3
TEX9	ENST00000537232.5 link	n.*1305+3021C>T		intron_variant	Intron 12 of 12	2		ENSP00000438745.2	A0A0S2Z6S1

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

GnomAD3 exomes

AF:

0.00140

AC:

352

AN:

250610

Hom.:

AF XY:

0.00157

AC XY:

213

AN XY:

135474

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 SAS exome

AF:

0.00409

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

Gnomad4 AFR exome

AF:

0.00102

Gnomad4 AMR exome

AF:

0.000897

Gnomad4 ASJ exome

AF:

0.00256

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00356

Gnomad4 FIN exome

AF:

0.0000750

Gnomad4 NFE exome

AF:

0.00149

Gnomad4 OTH exome

AF:

0.00177

GnomAD4 genome

AF:

0.00134

AC:

204

AN:

152226

Hom.:

Cov.:

AF XY:

0.00130

AC XY:

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.00128

Gnomad4 AMR

AF:

0.000851

Gnomad4 ASJ

AF:

0.00403

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00249

Gnomad4 FIN

AF:

0.0000944

Gnomad4 NFE

AF:

0.00159

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00143

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

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MNS1-related disorder

Benign:1

Feb 20, 2023

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.61

CADD

Benign

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

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

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