chrX-147944810-AC-A

Variant names:

• chrX-147944810-AC-A
• rs11293471
• NM_002024.6:c.1472-56delC

Variant summary

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

The NM_002024.6(FMR1):​c.1472-56delC 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. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 1.0 (38552 hom., 25601 hem., cov: 0)
  • Exomes 𝑓: 1.0 (357435 hom. 337010 hem.)
  • Failed GnomAD Quality Control
• Consequence: FMR1 NM_002024.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.233
• Publications: 3 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: Ambry Genetics, ClinGen, G2P, Orphanet, Labcorp Genetics (formerly Invitae), Myriad Women’s Health
• fragile X-associated tremor/ataxia syndrome

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

  Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002024.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FMR1	NM_002024.6	MANE Select	c.1472-56delC		intron	N/A	NP_002015.1	Q06787-1
	FMR1	NM_001185076.2		c.1409-56delC		intron	N/A	NP_001172005.1	Q06787-9
	FMR1	NM_001185082.2		c.1409-131delC		intron	N/A	NP_001172011.1	Q06787-8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FMR1	ENST00000370475.9	TSL:1 MANE Select	c.1472-56delC		intron	N/A	ENSP00000359506.5	Q06787-1
	FMR1	ENST00000218200.12	TSL:1	c.1409-56delC		intron	N/A	ENSP00000218200.8	Q06787-9
	FMR1	ENST00000439526.6	TSL:1	c.1403-56delC		intron	N/A	ENSP00000395923.2	G3V0J0

Frequencies

GnomAD3 genomes AF: 1.00 AC: 102698 AN: 102703 Hom.: 38557 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: 0.999

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 1.00

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.999 AC: 1052801 AN: 1053725 Hom.: 357435 Cov.: 0 AF XY: 1.00 AC XY: 337010 AN XY: 337011

African (AFR) AF: 0.999 AC: 24473 AN: 24506

American (AMR) AF: 0.997 AC: 30186 AN: 30263

Ashkenazi Jewish (ASJ) AF: 0.999 AC: 18077 AN: 18101

East Asian (EAS) AF: 0.999 AC: 29380 AN: 29411

South Asian (SAS) AF: 0.999 AC: 48491 AN: 48547

European-Finnish (FIN) AF: 0.999 AC: 37601 AN: 37655

Middle Eastern (MID) AF: 0.998 AC: 2910 AN: 2916

European-Non Finnish (NFE) AF: 0.999 AC: 817733 AN: 818338

Other (OTH) AF: 0.999 AC: 43950 AN: 43988

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 1.00 AC: 102710 AN: 102715 Hom.: 38552 Cov.: 0 AF XY: 1.00 AC XY: 25601 AN XY: 25601

African (AFR) AF: 1.00 AC: 28142 AN: 28143

American (AMR) AF: 1.00 AC: 9387 AN: 9387

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2524 AN: 2524

East Asian (EAS) AF: 1.00 AC: 3194 AN: 3194

South Asian (SAS) AF: 1.00 AC: 2069 AN: 2069

European-Finnish (FIN) AF: 0.999 AC: 4161 AN: 4164

Middle Eastern (MID) AF: 1.00 AC: 198 AN: 198

European-Non Finnish (NFE) AF: 1.00 AC: 50992 AN: 50993

Other (OTH) AF: 1.00 AC: 1379 AN: 1379

Alfa AF: 0.999 Hom.: 8060

Asia WGS AF: 0.997 AC: 2430 AN: 2438

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.23
La Branchor		0.55
BranchPoint Hunter		4.0
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: rs11293471; hg19: chrX-147026330;