NM_145246.5:c.-163_-149delCGGCGGCGGCGGCGG

Variant names:

• chr10-93702522-ACCGCCGCCGCCGCCG-A
• rs139811637
• NM_145246.5:c.-163_-149delCGGCGGCGGCGGCGG

Variant summary

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

The NM_145246.5(FRA10AC1):​c.-163_-149delCGGCGGCGGCGGCGG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000139 in 215,916 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.0000068 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000029 (0 hom.)
• Consequence: FRA10AC1 NM_145246.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08
• Publications: 1 publications found

Genes affected

FRA10AC1 (HGNC:1162): (FRA10A associated CGG repeat 1) The protein encoded by this gene is a nuclear phosphoprotein of unknown function. This gene contains a tandem CGG repeat region within a CpG island that normally consists of 8-14 repeats but can expand to over 200 repeats. The repeat region is within the 5' UTR of some transcript variants, but is intronic to another variant. The expanded repeat allele is a fragile site and becomes hypermethylated, causing a reduction in gene expression. A disease phenotype has not been associated with expanded alleles. This gene is found within the rare FRA10A folate-sensitive fragile site. [provided by RefSeq, Dec 2016]

FRA10AC1 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with growth retardation, dysmorphic facies, and corpus callosum abnormalities

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, G2P

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145246.5. 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
	FRA10AC1	NM_145246.5	MANE Select	c.-163_-149delCGGCGGCGGCGGCGG		5_prime_UTR	Exon 1 of 14	NP_660289.2
	FRA10AC1	NM_001347712.2		c.-364_-350delCGGCGGCGGCGGCGG		5_prime_UTR	Exon 1 of 14	NP_001334641.1	Q70Z53-1
	FRA10AC1	NM_001347713.2		c.-283_-269delCGGCGGCGGCGGCGG		5_prime_UTR	Exon 1 of 15	NP_001334642.1	Q70Z53-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRA10AC1	ENST00000359204.5	TSL:1 MANE Select	c.-163_-149delCGGCGGCGGCGGCGG		5_prime_UTR	Exon 1 of 14	ENSP00000360488.3	Q70Z53-1
	FRA10AC1	ENST00000959343.1		c.-163_-149delCGGCGGCGGCGGCGG		5_prime_UTR	Exon 1 of 14	ENSP00000629402.1
	FRA10AC1	ENST00000905754.1		c.-364_-350delCGGCGGCGGCGGCGG		5_prime_UTR	Exon 1 of 14	ENSP00000575813.1

Frequencies

GnomAD3 genomes AF: 0.00000679 AC: 1 AN: 147320 Hom.: 0 Cov.: 0

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: 0.0000151

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000292 AC: 2 AN: 68596 Hom.: 0 AF XY: 0.0000233 AC XY: 1 AN XY: 42838

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 1018

American (AMR) AF: 0.00 AC: 0 AN: 2066

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 976

East Asian (EAS) AF: 0.00 AC: 0 AN: 1204

South Asian (SAS) AF: 0.0000807 AC: 1 AN: 12396

European-Finnish (FIN) AF: 0.000359 AC: 1 AN: 2786

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 228

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 44554

Other (OTH) AF: 0.00 AC: 0 AN: 3368

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00000679 AC: 1 AN: 147320 Hom.: 0 Cov.: 0 AF XY: 0.0000139 AC XY: 1 AN XY: 71720

African (AFR) AF: 0.00 AC: 0 AN: 39890

American (AMR) AF: 0.00 AC: 0 AN: 14892

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3396

East Asian (EAS) AF: 0.00 AC: 0 AN: 5022

South Asian (SAS) AF: 0.00 AC: 0 AN: 4586

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9900

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 302

European-Non Finnish (NFE) AF: 0.0000151 AC: 1 AN: 66422

Other (OTH) AF: 0.00 AC: 0 AN: 2006

Alfa AF: 0.00 Hom.: 649

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1

Splicing

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

Other links and lift over

dbSNP: rs139811637; hg19: chr10-95462279;