Genetic Variant MSGN1:p.Arg5Ser (chr2-17816531-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001105569.3(MSGN1):c.13C>A(p.Arg5Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000181 in 1,436,904 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

MSGN1
NM_001105569.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.76

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.062342077).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSGN1	NM_001105569.3 link	c.13C>A	p.Arg5Ser	missense_variant	Exon 1 of 1	ENST00000281047.4	NP_001099039.1	A6NI15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSGN1	ENST00000281047.4 link	c.13C>A	p.Arg5Ser	missense_variant	Exon 1 of 1	6	NM_001105569.3	ENSP00000281047.3		A6NI15

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000252

AC:

AN:

237888

Hom.:

AF XY:

0.0000309

AC XY:

AN XY:

129574

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000205

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000181

AC:

AN:

1436904

Hom.:

Cov.:

AF XY:

0.0000211

AC XY:

AN XY:

710946

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000295

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000169

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000248

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 31, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.13C>A (p.R5S) alteration is located in exon 1 (coding exon 1) of the MSGN1 gene. This alteration results from a C to A substitution at nucleotide position 13, causing the arginine (R) at amino acid position 5 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.62

CADD

Benign

8.4

DANN

Benign

0.90

DEOGEN2

Benign

0.064

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.68

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.47

M_CAP

Benign

0.0065

MetaRNN

Benign

0.062

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.40

REVEL

Benign

0.042

Sift

Benign

0.11

Sift4G

Benign

0.15

Polyphen

0.0060

Vest4

0.29

MutPred

0.18

Loss of helix (P = 0.0237);

MVP

0.12

MPC

0.16

ClinPred

0.036

GERP RS

2.5

Varity_R

0.085

gMVP

0.38

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