2-17816986-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001105569.3(MSGN1):​c.468C>G​(p.Ser156Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000212 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

MSGN1
NM_001105569.3 missense

Scores

8
6
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.65
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.8

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MSGN1NM_001105569.3 linkc.468C>G p.Ser156Arg 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
MSGN1ENST00000281047.4 linkc.468C>G p.Ser156Arg missense_variant Exon 1 of 1 6 NM_001105569.3 ENSP00000281047.3 A6NI15

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
249452
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135382
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:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000265
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000212
AC:
31
AN:
1461882
Hom.:
0
Cov.:
73
AF XY:
0.0000234
AC XY:
17
AN XY:
727238
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000671
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000252
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.00000826
AC:
1
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 13, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.468C>G (p.S156R) alteration is located in exon 1 (coding exon 1) of the MSGN1 gene. This alteration results from a C to G substitution at nucleotide position 468, causing the serine (S) at amino acid position 156 to be replaced by an arginine (R). 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
Pathogenic
0.97
BayesDel_addAF
Pathogenic
0.23
D
BayesDel_noAF
Pathogenic
0.15
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.88
D
Eigen
Benign
0.16
Eigen_PC
Benign
0.13
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Benign
0.84
T
M_CAP
Pathogenic
0.37
D
MetaRNN
Pathogenic
0.80
D
MetaSVM
Pathogenic
0.83
D
MutationAssessor
Benign
1.4
L
PrimateAI
Uncertain
0.68
T
PROVEAN
Uncertain
-3.2
D
REVEL
Pathogenic
0.74
Sift
Uncertain
0.0020
D
Sift4G
Uncertain
0.0040
D
Polyphen
1.0
D
Vest4
0.58
MutPred
0.48
Gain of MoRF binding (P = 0.0147);
MVP
0.75
MPC
0.65
ClinPred
0.92
D
GERP RS
2.3
Varity_R
0.68
gMVP
0.76

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs771372109; hg19: chr2-17998253; API