chr10-93702522-ACCGCCGCCG-A

Position:

• chr10-93702522-ACCGCCGCCG-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000359204.5(FRA10AC1):​c.-157_-149del 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 ENST00000359204.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRA10AC1	NM_145246.5	c.-157_-149del		5_prime_UTR_variant	1/14	ENST00000359204.5	NP_660289.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FRA10AC1	ENST00000359204.5	c.-157_-149del		5_prime_UTR_variant	1/14	1	NM_145246.5	ENSP00000360488	P1

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

Gnomad4 AFR exome AF: 0.00197

Gnomad4 AMR exome AF: 0.000484

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000161

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000112

Gnomad4 OTH exome AF: 0.000297

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

Gnomad4 AFR AF: 0.000650

Gnomad4 AMR AF: 0.000134

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000211

Gnomad4 OTH AF: 0.000493

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs139811637; hg19: chr10-95462279;