Variant rs797045582 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_002024.6(FMR1):c.374C>T(p.Thr125Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000456 in 1,097,158 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0000046 ( 0 hom. 2 hem. )

Consequence

FMR1
NM_002024.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.98

Variant links:

Genes affected

FMR1 (HGNC:3775): (fragile X messenger ribonucleoprotein 1) The protein encoded by this gene binds RNA and is associated with polysomes. The encoded protein may be involved in mRNA trafficking from the nucleus to the cytoplasm. A trinucleotide repeat (CGG) in the 5' UTR is normally found at 6-53 copies, but an expansion to 55-230 repeats is the cause of fragile X syndrome. Expansion of the trinucleotide repeat may also cause one form of premature ovarian failure (POF1). Multiple alternatively spliced transcript variants that encode different protein isoforms and which are located in different cellular locations have been described for this gene. [provided by RefSeq, May 2010]

FMR1 links:

FMR1 (HGNC:):

FMR1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.4223452).

BS2

High Hemizygotes in GnomAdExome4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FMR1	NM_002024.6 linkuse as main transcript	c.374C>T	p.Thr125Ile	missense_variant	5/17	ENST00000370475.9	NP_002015.1	Q06787-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FMR1	ENST00000370475.9 linkuse as main transcript	c.374C>T	p.Thr125Ile	missense_variant	5/17	1	NM_002024.6	ENSP00000359506.5		Q06787-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000546

AC:

AN:

183152

Hom.:

AF XY:

0.00

AC XY:

AN XY:

67694

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:

0.0000122

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000456

AC:

AN:

1097158

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

362662

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:

0.00000594

Gnomad4 OTH exome

AF:

0.00

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

Genetic Services Laboratory, University of Chicago

Jun 29, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.70

BayesDel_addAF

Benign

-0.0031

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.17

T;.;.;.;.;T;T;.;D;T;T;.

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.90

D;D;D;D;D;D;.;D;D;D;D;D

M_CAP

Benign

0.055

MetaRNN

Benign

0.42

T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.53

MutationAssessor

Uncertain

2.3

.;M;M;M;.;.;.;.;M;.;.;M

PrimateAI

Uncertain

0.64

PROVEAN

Pathogenic

-4.6

.;D;D;.;D;.;D;D;D;.;.;D

REVEL

Benign

0.22

Sift

Uncertain

0.0030

.;D;T;.;D;.;D;T;T;.;.;T

Sift4G

Uncertain

0.0090

D;D;D;D;D;D;D;D;D;D;D;D

Polyphen

0.99, 0.47, 0.99, 0.99

.;.;.;D;.;P;P;D;D;.;.;.

Vest4

0.85

MutPred

0.28

Loss of disorder (P = 0.0495);Loss of disorder (P = 0.0495);Loss of disorder (P = 0.0495);Loss of disorder (P = 0.0495);Loss of disorder (P = 0.0495);Loss of disorder (P = 0.0495);Loss of disorder (P = 0.0495);Loss of disorder (P = 0.0495);Loss of disorder (P = 0.0495);Loss of disorder (P = 0.0495);.;Loss of disorder (P = 0.0495);

MVP

0.86

MPC

2.0

ClinPred

0.94

GERP RS

5.3

Varity_R

0.81

gMVP

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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