chrX-147912049-CGCGGCGGCGGCGGCG-C

Variant names:

• chrX-147912048-GCGCGGCGGCGGCGGC-GC
• NM_002024.6:c.-129_-116delCGGCGGCGGCGGCG

Variant summary

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

The NM_002024.6(FMR1):​c.-129_-116delCGGCGGCGGCGGCG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 2)
• Consequence: FMR1 NM_002024.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.66
• Publications: 0 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-AS1 (HGNC:39081): (FMR1 antisense RNA 1)

ENSG00000274086 (HGNC:):

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.-129_-116delCGGCGGCGGCGGCG		5_prime_UTR	Exon 1 of 17	NP_002015.1	Q06787-1
	FMR1	NM_001185076.2		c.-129_-116delCGGCGGCGGCGGCG		5_prime_UTR	Exon 1 of 16	NP_001172005.1	Q06787-9
	FMR1	NM_001185082.2		c.-129_-116delCGGCGGCGGCGGCG		5_prime_UTR	Exon 1 of 16	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.-129_-116delCGGCGGCGGCGGCG		5_prime_UTR	Exon 1 of 17	ENSP00000359506.5	Q06787-1
	FMR1	ENST00000218200.12	TSL:1	c.-129_-116delCGGCGGCGGCGGCG		5_prime_UTR	Exon 1 of 16	ENSP00000218200.8	Q06787-9
	FMR1	ENST00000439526.6	TSL:1	c.-129_-116delCGGCGGCGGCGGCG		5_prime_UTR	Exon 1 of 16	ENSP00000395923.2	G3V0J0

Frequencies

GnomAD3 genomes Cov.: 2

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

GnomAD4 genome Cov.: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.7

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chrX-146993566;