rs11342854

Variant names:

• chrX-147941703-TC-T
• rs11342854
• NM_002024.6:c.1275+1042delC

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_002024.6(FMR1):​c.1275+1042delC variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 1.0 (38923 hom., 33170 hem., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: FMR1 NM_002024.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• fragile X syndrome

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Myriad Women’s Health, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
• fragile X-associated tremor/ataxia syndrome

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P, Ambry Genetics
• premature ovarian failure 1

  Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• symptomatic form of fragile X syndrome in female carrier

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FMR1	NM_002024.6	c.1275+1042delC		intron_variant	Intron 13 of 16	ENST00000370475.9	NP_002015.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FMR1	ENST00000370475.9	c.1275+1042delC		intron_variant	Intron 13 of 16	1	NM_002024.6	ENSP00000359506.5

Frequencies

GnomAD3 genomes AF: 1.00 AC: 110970 AN: 110971 Hom.: 38928 Cov.: 0

Gnomad AFR AF: 1.00

Gnomad AMI AF: 1.00

Gnomad AMR AF: 1.00

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 1.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 1.00 AC: 111016 AN: 111017 Hom.: 38923 Cov.: 0 AF XY: 1.00 AC XY: 33170 AN XY: 33171

African (AFR) AF: 1.00 AC: 30563 AN: 30563

American (AMR) AF: 1.00 AC: 10492 AN: 10492

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2646 AN: 2646

East Asian (EAS) AF: 1.00 AC: 3505 AN: 3505

South Asian (SAS) AF: 1.00 AC: 2620 AN: 2620

European-Finnish (FIN) AF: 1.00 AC: 5775 AN: 5775

Middle Eastern (MID) AF: 1.00 AC: 217 AN: 217

European-Non Finnish (NFE) AF: 1.00 AC: 53024 AN: 53025

Other (OTH) AF: 1.00 AC: 1494 AN: 1494

Alfa AF: 0.857 Hom.: 2235

Asia WGS AF: 1.00 AC: 2522 AN: 2522

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11342854; hg19: chrX-147023222;