Variant 7-30146289-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_152793.3(MTURN):c.275C>A(p.Ser92Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,908 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

MTURN
NM_152793.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.88

Variant links:

Genes affected

MTURN (HGNC:25457): (maturin, neural progenitor differentiation regulator homolog) Involved in negative regulation of NF-kappaB transcription factor activity; positive regulation of MAPK cascade; and positive regulation of megakaryocyte differentiation. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MTURN 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
MTURN	NM_152793.3 linkuse as main transcript	c.275C>A	p.Ser92Tyr	missense_variant	2/3	ENST00000324453.13	NP_690006.2
MTURN	XM_005249652.4 linkuse as main transcript	c.275C>A	p.Ser92Tyr	missense_variant	2/4		XP_005249709.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTURN	ENST00000324453.13 linkuse as main transcript	c.275C>A	p.Ser92Tyr	missense_variant	2/3	1	NM_152793.3	ENSP00000324204	P1	Q8N3F0-1
MTURN	ENST00000324489.5 linkuse as main transcript	c.176C>A	p.Ser59Tyr	missense_variant	2/3	1		ENSP00000324755		Q8N3F0-3
MTURN	ENST00000434060.1 linkuse as main transcript	c.224C>A	p.Ser75Tyr	missense_variant	2/2	2		ENSP00000415658
MTURN	ENST00000409688.1 linkuse as main transcript	c.162+10991C>A		intron_variant		2		ENSP00000386490		Q8N3F0-4

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461692

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727122

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152216

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

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:

0.00

Bravo

AF:

0.00000378

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

May 15, 2023

The c.275C>A (p.S92Y) alteration is located in exon 2 (coding exon 2) of the MTURN gene. This alteration results from a C to A substitution at nucleotide position 275, causing the serine (S) at amino acid position 92 to be replaced by a tyrosine (Y). 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

0.74

BayesDel_addAF

Uncertain

0.088

BayesDel_noAF

Benign

-0.11

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

T;.;.

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.89

D;D;D

M_CAP

Benign

0.019

MetaRNN

Uncertain

0.47

T;T;T

MetaSVM

Benign

-0.64

MutationAssessor

Benign

0.55

N;.;.

MutationTaster

Benign

1.0

D;D;D;D;D

PROVEAN

Pathogenic

-4.4

D;D;D

REVEL

Uncertain

0.49

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.011

D;D;D

Polyphen

0.23

B;.;.

Vest4

0.60

MutPred

0.26

Loss of disorder (P = 0.0528);.;.;

MVP

0.15

MPC

1.4

ClinPred

0.99

GERP RS

5.5

Varity_R

0.80

gMVP

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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