chr2-17816828-C-T

Position:

• chr2-17816828-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.43 (16389 hom., cov: 33)
  • Exomes 𝑓: 0.53 (218938 hom.)
• Consequence: MSGN1 NM_001105569.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.26

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSGN1	NM_001105569.3	c.310C>T	p.His104Tyr	missense_variant	1/1	ENST00000281047.4	NP_001099039.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSGN1	ENST00000281047.4	c.310C>T	p.His104Tyr	missense_variant	1/1		NM_001105569.3	ENSP00000281047	P1

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65865 AN: 152036 Hom.: 16390 Cov.: 33

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

GnomAD3 exomes AF: 0.452 AC: 112602 AN: 249042 Hom.: 29245 AF XY: 0.467 AC XY: 63197 AN XY: 135182

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 SAS exome AF: 0.482

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.: 76 AF XY: 0.537 AC XY: 390151 AN XY: 727206

Gnomad4 AFR exome AF: 0.236

Gnomad4 AMR exome AF: 0.305

Gnomad4 ASJ exome AF: 0.630

Gnomad4 EAS exome AF: 0.0301

Gnomad4 SAS exome AF: 0.485

Gnomad4 FIN exome AF: 0.436

Gnomad4 NFE exome AF: 0.578

Gnomad4 OTH exome AF: 0.516

GnomAD4 genome AF: 0.433 AC: 65861 AN: 152154 Hom.: 16389 Cov.: 33 AF XY: 0.424 AC XY: 31548 AN XY: 74388

Gnomad4 AFR AF: 0.245

Gnomad4 AMR AF: 0.387

Gnomad4 ASJ AF: 0.620

Gnomad4 EAS AF: 0.0269

Gnomad4 SAS AF: 0.443

Gnomad4 FIN AF: 0.429

Gnomad4 NFE AF: 0.573

Gnomad4 OTH AF: 0.474

Alfa AF: 0.541 Hom.: 36462

Bravo AF: 0.417

TwinsUK AF: 0.573 AC: 2124

ALSPAC AF: 0.570 AC: 2196

ESP6500AA AF: 0.249 AC: 1015

ESP6500EA AF: 0.573 AC: 4794

ExAC AF: 0.453 AC: 54844

EpiCase AF: 0.594

EpiControl AF: 0.592

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.043
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.5
DANN	Benign	0.27
DEOGEN2	Benign	0.032	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0062	N
LIST_S2	Benign	0.22	T
MetaRNN	Benign	0.000030	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-2.0	N
MutationTaster	Benign	1.0	P
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	0.82	N
REVEL	Benign	0.073
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.063
MPC		0.17
ClinPred		0.0068	T
GERP RS		5.8
Varity_R		0.022
gMVP		0.33

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

Publications

LitVar

Other links and lift over

dbSNP: rs35858730; hg19: chr2-17998095; COSMIC: COSV55262932;