chr10-93702522-A-ACCGCCGCCGCCGCCGCCGCCGCCG

Variant names:

• chr10-93702522-A-ACCGCCGCCGCCGCCGCCGCCGCCG
• rs139811637
• NM_145246.5:c.-172_-149dupCGGCGGCGGCGGCGGCGGCGGCGG

Variant summary

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

The NM_145246.5(FRA10AC1):​c.-172_-149dupCGGCGGCGGCGGCGGCGGCGGCGG 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 INS_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 0.000088 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00010 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: FRA10AC1 NM_145246.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03
• 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.-172_-149dupCGGCGGCGGCGGCGGCGGCGGCGG		5_prime_UTR	Exon 1 of 14	NP_660289.2
	FRA10AC1	NM_001347712.2		c.-373_-350dupCGGCGGCGGCGGCGGCGGCGGCGG		5_prime_UTR	Exon 1 of 14	NP_001334641.1	Q70Z53-1
	FRA10AC1	NM_001347713.2		c.-292_-269dupCGGCGGCGGCGGCGGCGGCGGCGG		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.-172_-149dupCGGCGGCGGCGGCGGCGGCGGCGG		5_prime_UTR	Exon 1 of 14	ENSP00000360488.3	Q70Z53-1
	FRA10AC1	ENST00000959343.1		c.-172_-149dupCGGCGGCGGCGGCGGCGGCGGCGG		5_prime_UTR	Exon 1 of 14	ENSP00000629402.1
	FRA10AC1	ENST00000905754.1		c.-373_-350dupCGGCGGCGGCGGCGGCGGCGGCGG		5_prime_UTR	Exon 1 of 14	ENSP00000575813.1

Frequencies

GnomAD3 genomes AF: 0.0000882 AC: 13 AN: 147318 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000100

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000672

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000218

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000105

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000102 AC: 7 AN: 68614 Hom.: 1 Cov.: 0 AF XY: 0.0000933 AC XY: 4 AN XY: 42852

⚠️ 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: 1206

South Asian (SAS) AF: 0.00 AC: 0 AN: 12402

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2786

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

European-Non Finnish (NFE) AF: 0.000157 AC: 7 AN: 44564

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: 0.0000882 AC: 13 AN: 147434 Hom.: 0 Cov.: 0 AF XY: 0.0000696 AC XY: 5 AN XY: 71842

African (AFR) AF: 0.000100 AC: 4 AN: 40004

American (AMR) AF: 0.0000671 AC: 1 AN: 14912

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5010

South Asian (SAS) AF: 0.000218 AC: 1 AN: 4582

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 284

European-Non Finnish (NFE) AF: 0.000105 AC: 7 AN: 66414

Other (OTH) AF: 0.00 AC: 0 AN: 2028

Alfa AF: 0.00 Hom.: 649

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.0

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;