3-52833728-T-C

Position:

chr3-52833728-T-C

Variant summary

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

The NM_205853.4(MUSTN1):c.31A>G(p.Ile11Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000124 in 1,585,138 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00045 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000089 ( 0 hom. )

Consequence

MUSTN1
NM_205853.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.33

Variant links:

Genes affected

MUSTN1 (HGNC:22144): (musculoskeletal, embryonic nuclear protein 1) Predicted to be involved in several processes, including chondrocyte differentiation; chondrocyte proliferation; and embryonic limb morphogenesis. Predicted to act upstream of or within positive regulation of chondrocyte differentiation; positive regulation of chondrocyte proliferation; and positive regulation of macromolecule metabolic process. Predicted to be located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MUSTN1 links:

STIMATE-MUSTN1 (HGNC:38834): (STIMATE-MUSTN1 readthrough) This locus represents naturally occurring read-through transcription between the neighboring TMEM110 (transmembrane protein 110) and MUSTN1 (musculoskeletal, embryonic nuclear protein 1) genes. The read-through transcript encodes a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Nov 2010]

STIMATE-MUSTN1 links:

ENSG00000243696 (HGNC:):

ENSG00000243696 links:

Genome browser will be placed here

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=0.00978899).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUSTN1	NM_205853.4 link	c.31A>G	p.Ile11Val	missense_variant	2/3	ENST00000446157.3	NP_995325.4	Q8IVN3
STIMATE-MUSTN1	NM_001198974.3 link	c.901A>G	p.Ile301Val	missense_variant	9/10		NP_001185903.2	A8MSY1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MUSTN1	ENST00000446157.3 link	c.31A>G	p.Ile11Val	missense_variant	2/3	1	NM_205853.4	ENSP00000410910.2	Q8IVN3
STIMATE-MUSTN1	ENST00000504329.1 link	c.901A>G	p.Ile301Val	missense_variant	9/10	5		ENSP00000422941.1	A8MSY1
ENSG00000243696	ENST00000468472.1 link	n.31A>G		non_coding_transcript_exon_variant	2/24	2		ENSP00000422253.1	D6R8Y8

Frequencies

GnomAD3 genomes

AF:

0.000454

AC:

AN:

152074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00150

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.000138

AC:

AN:

202284

Hom.:

AF XY:

0.000157

AC XY:

AN XY:

108510

show subpopulations

Gnomad AFR exome

AF:

0.000859

Gnomad AMR exome

AF:

0.000376

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:

0.0000568

Gnomad OTH exome

AF:

0.000381

GnomAD4 exome

AF:

0.0000893

AC:

128

AN:

1432946

Hom.:

Cov.:

AF XY:

0.0000916

AC XY:

AN XY:

709918

show subpopulations

Gnomad4 AFR exome

AF:

0.00195

Gnomad4 AMR exome

AF:

0.000372

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:

0.0000210

Gnomad4 OTH exome

AF:

0.000420

GnomAD4 genome

AF:

0.000453

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.000443

AC XY:

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.00152

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000475

Alfa

AF:

0.0000680

Hom.:

Bravo

AF:

0.000540

ESP6500AA

AF:

0.00160

AC:

ESP6500EA

AF:

0.000122

AC:

ExAC

AF:

0.000125

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 03, 2022

The c.901A>G (p.I301V) alteration is located in exon 9 (coding exon 9) of the TMEM110-MUSTN1 gene. This alteration results from a A to G substitution at nucleotide position 901, causing the isoleucine (I) at amino acid position 301 to be replaced by a valine (V). 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

0.071

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0037

.;T;.

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.81

T;T;T

M_CAP

Benign

0.0020

MetaRNN

Benign

0.0098

T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.090

N;N;N

REVEL

Benign

0.024

Sift

Benign

0.48

T;T;T

Sift4G

Benign

0.95

T;T;T

Polyphen

0.0010, 0.0

.;B;B

Vest4

0.13

MVP

0.014

MPC

0.018, 0.076

ClinPred

0.011

GERP RS

2.7

Varity_R

0.024

gMVP

0.046

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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