10-93702522-ACCGCCGCCGCCGCCGCCG-ACCGCCGCCG

Variant names:

• chr10-93702522-ACCGCCGCCG-A
• rs139811637
• NM_145246.5:c.-157_-149delCGGCGGCGG

Variant summary

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

The NM_145246.5(FRA10AC1):​c.-157_-149delCGGCGGCGG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00025 in 215,994 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00029 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00016 (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.-157_-149delCGGCGGCGG		5_prime_UTR	Exon 1 of 14	NP_660289.2
	FRA10AC1	NM_001347712.2		c.-358_-350delCGGCGGCGG		5_prime_UTR	Exon 1 of 14	NP_001334641.1	Q70Z53-1
	FRA10AC1	NM_001347713.2		c.-277_-269delCGGCGGCGG		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.-157_-149delCGGCGGCGG		5_prime_UTR	Exon 1 of 14	ENSP00000360488.3	Q70Z53-1
	FRA10AC1	ENST00000959343.1		c.-157_-149delCGGCGGCGG		5_prime_UTR	Exon 1 of 14	ENSP00000629402.1
	FRA10AC1	ENST00000905754.1		c.-358_-350delCGGCGGCGG		5_prime_UTR	Exon 1 of 14	ENSP00000575813.1

Frequencies

GnomAD3 genomes AF: 0.000292 AC: 43 AN: 147320 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000652

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000134

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: 0.000211

Gnomad OTH AF: 0.000499

GnomAD4 exome AF: 0.000160 AC: 11 AN: 68558 Hom.: 0 AF XY: 0.000163 AC XY: 7 AN XY: 42816

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

African (AFR) AF: 0.00197 AC: 2 AN: 1016

American (AMR) AF: 0.000484 AC: 1 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: 0.000161 AC: 2 AN: 12394

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2784

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

European-Non Finnish (NFE) AF: 0.000112 AC: 5 AN: 44524

Other (OTH) AF: 0.000297 AC: 1 AN: 3364

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000000000000467404), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000292 AC: 43 AN: 147436 Hom.: 0 Cov.: 0 AF XY: 0.000306 AC XY: 22 AN XY: 71844

African (AFR) AF: 0.000650 AC: 26 AN: 40006

American (AMR) AF: 0.000134 AC: 2 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: 0.00 AC: 0 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: 0.000211 AC: 14 AN: 66414

Other (OTH) AF: 0.000493 AC: 1 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		1.1
Mutation Taster		=300/0	polymorphism

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;