Variant 3-52833397-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_205853.4(MUSTN1):c.176G>C(p.Ser59Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000616 in 1,461,508 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

MUSTN1
NM_205853.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.17

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUSTN1	NM_205853.4 linkuse as main transcript	c.176G>C	p.Ser59Thr	missense_variant	3/3	ENST00000446157.3	NP_995325.4	Q8IVN3
STIMATE-MUSTN1	NM_001198974.3 linkuse as main transcript	c.1046G>C	p.Ser349Thr	missense_variant	10/10		NP_001185903.2	A8MSY1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MUSTN1	ENST00000446157.3 linkuse as main transcript	c.176G>C	p.Ser59Thr	missense_variant	3/3	1	NM_205853.4	ENSP00000410910.2	Q8IVN3
STIMATE-MUSTN1	ENST00000504329.1 linkuse as main transcript	c.1046G>C	p.Ser349Thr	missense_variant	10/10	5		ENSP00000422941.1	A8MSY1
ENSG00000243696	ENST00000468472.1 linkuse as main transcript	n.176G>C		non_coding_transcript_exon_variant	3/24	2		ENSP00000422253.1	D6R8Y8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461508

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

727018

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:

0.0000927

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

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

Mar 20, 2024

The c.1046G>C (p.S349T) alteration is located in exon 10 (coding exon 10) of the TMEM110-MUSTN1 gene. This alteration results from a G to C substitution at nucleotide position 1046, causing the serine (S) at amino acid position 349 to be replaced by a threonine (T). 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

0.28

BayesDel_addAF

Uncertain

0.051

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

.;T;.

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.89

D;D;D

M_CAP

Benign

0.042

MetaRNN

Benign

0.25

T;T;T

MetaSVM

Uncertain

-0.28

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-3.0

D;D;N

REVEL

Benign

0.19

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.99, 0.92

.;D;P

Vest4

0.43

MutPred

0.34

.;.;Gain of glycosylation at T353 (P = 0.0085);

MVP

0.014

MPC

0.15, 0.44

ClinPred

0.98

GERP RS

4.9

Varity_R

0.12

gMVP

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.26

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.26

Position offset: -15

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over