Genetic Variant MSGN1:p.His104Tyr (chr2-17816828-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001105569.3(MSGN1):c.310C>T(p.His104Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 1,613,978 control chromosomes in the GnomAD database, including 235,327 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.43 ( 16389 hom., cov: 33)

Exomes 𝑓: 0.53 ( 218938 hom. )

Consequence

MSGN1
NM_001105569.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.26

Publications

24 publications found

Variant links:

Genes affected

MSGN1 (HGNC:14907): (mesogenin 1) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in mesoderm formation and regulation of transcription by RNA polymerase II. Predicted to act upstream of or within segment specification and somitogenesis. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

MSGN1 Gene-Disease associations (from GenCC):

skeletal dysplasia
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

MSGN1 links:

ENSG00000297720 (HGNC:):

ENSG00000297720 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001105569.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.0464262E-5).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001105569.3. 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
	MSGN1	NM_001105569.3	MANE Select	c.310C>T	p.His104Tyr	missense	Exon 1 of 1	NP_001099039.1	A6NI15

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MSGN1	ENST00000281047.4	TSL:6 MANE Select	c.310C>T	p.His104Tyr	missense	Exon 1 of 1	ENSP00000281047.3	A6NI15
ENSG00000297720	ENST00000750479.1		n.454-11874G>A		intron	N/A
ENSG00000297720	ENST00000750480.1		n.416-8095G>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.433

AC:

65865

AN:

152036

Hom.:

16390

Cov.:

show subpopulations

Gnomad AFR

AF:

0.246

Gnomad AMI

AF:

0.720

Gnomad AMR

AF:

0.387

Gnomad ASJ

AF:

0.620

Gnomad EAS

AF:

0.0268

Gnomad SAS

AF:

0.442

Gnomad FIN

AF:

0.429

Gnomad MID

AF:

0.712

Gnomad NFE

AF:

0.573

Gnomad OTH

AF:

0.478

GnomAD2 exomes

AF:

0.452

AC:

112602

AN:

249042

AF XY:

0.467

show subpopulations

Gnomad AFR exome

AF:

0.241

Gnomad AMR exome

AF:

0.292

Gnomad ASJ exome

AF:

0.638

Gnomad EAS exome

AF:

0.0216

Gnomad FIN exome

AF:

0.441

Gnomad NFE exome

AF:

0.573

Gnomad OTH exome

AF:

0.509

GnomAD4 exome

AF:

0.535

AC:

781703

AN:

1461824

Hom.:

218938

Cov.:

AF XY:

0.537

AC XY:

390151

AN XY:

727206

show subpopulations

African (AFR)

AF:

0.236

AC:

7904

AN:

33480

American (AMR)

AF:

0.305

AC:

13658

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.630

AC:

16474

AN:

26136

East Asian (EAS)

AF:

0.0301

AC:

1193

AN:

39700

South Asian (SAS)

AF:

0.485

AC:

41858

AN:

86254

European-Finnish (FIN)

AF:

0.436

AC:

23308

AN:

53406

Middle Eastern (MID)

AF:

0.677

AC:

3906

AN:

5768

European-Non Finnish (NFE)

AF:

0.578

AC:

642264

AN:

1111968

Other (OTH)

AF:

0.516

AC:

31138

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

23527

47054

70582

94109

117636

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17306

34612

51918

69224

86530

<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:

0.433

AC:

65861

AN:

152154

Hom.:

16389

Cov.:

AF XY:

0.424

AC XY:

31548

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.245

AC:

10195

AN:

41528

American (AMR)

AF:

0.387

AC:

5913

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.620

AC:

2152

AN:

3470

East Asian (EAS)

AF:

0.0269

AC:

139

AN:

5176

South Asian (SAS)

AF:

0.443

AC:

2132

AN:

4816

European-Finnish (FIN)

AF:

0.429

AC:

4543

AN:

10600

Middle Eastern (MID)

AF:

0.721

AC:

212

AN:

294

European-Non Finnish (NFE)

AF:

0.573

AC:

38920

AN:

67958

Other (OTH)

AF:

0.474

AC:

1000

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1725

3451

5176

6902

8627

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

596

1192

1788

2384

2980

<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:

0.525

Hom.:

43675

Bravo

AF:

0.417

EpiCase

AF:

0.594

EpiControl

AF:

0.592

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.043

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.5

(source)

DANN

Benign

0.27

DEOGEN2

Benign

0.032

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.0062

LIST_S2

Benign

0.22

MetaRNN

Benign

0.000030

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-2.0

PhyloP100

1.3

PrimateAI

Uncertain

0.55

PROVEAN

Benign

0.82

REVEL

Benign

0.073

Sift

Benign

1.0

Sift4G

Benign

1.0

PromoterAI

0.019

Neutral

(source)

Varity_R

0.022

gMVP

0.33

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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