Genetic Variant FRA10AC1:c.-160_-149dupCGGCGGCGGCGG (chr10-93702522-A-ACCGCCGCCGCCG) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_145246.5(FRA10AC1):c.-160_-149dupCGGCGGCGGCGG 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 0.000068 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00015 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

FRA10AC1
NM_145246.5 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.03

Publications

1 publications found

Variant links:

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

FRA10AC1 links:

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ACMG classification

Classification was made for transcript

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FRA10AC1	NM_145246.5	MANE Select	c.-160_-149dupCGGCGGCGGCGG	5_prime_UTR	Exon 1 of 14	NP_660289.2
FRA10AC1	NM_001347712.2		c.-361_-350dupCGGCGGCGGCGG	5_prime_UTR	Exon 1 of 14	NP_001334641.1	Q70Z53-1
FRA10AC1	NM_001347713.2		c.-280_-269dupCGGCGGCGGCGG	5_prime_UTR	Exon 1 of 15	NP_001334642.1	Q70Z53-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FRA10AC1	ENST00000359204.5	TSL:1 MANE Select	c.-160_-149dupCGGCGGCGGCGG	5_prime_UTR	Exon 1 of 14	ENSP00000360488.3	Q70Z53-1
FRA10AC1	ENST00000959343.1		c.-160_-149dupCGGCGGCGGCGG	5_prime_UTR	Exon 1 of 14	ENSP00000629402.1
FRA10AC1	ENST00000905754.1		c.-361_-350dupCGGCGGCGGCGG	5_prime_UTR	Exon 1 of 14	ENSP00000575813.1

Frequencies

GnomAD3 genomes

AF:

0.0000679

AC:

AN:

147316

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000175

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000199

Gnomad SAS

AF:

0.000218

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000151

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000146

AC:

AN:

68594

Hom.:

Cov.:

AF XY:

0.000140

AC XY:

AN XY:

42846

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

1018

American (AMR)

AF:

0.00

AC:

AN:

2064

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

976

East Asian (EAS)

AF:

0.00250

AC:

AN:

1202

South Asian (SAS)

AF:

0.000161

AC:

AN:

12402

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2784

Middle Eastern (MID)

AF:

0.00

AC:

AN:

228

European-Non Finnish (NFE)

AF:

0.000112

AC:

AN:

44554

Other (OTH)

AF:

0.00

AC:

AN:

3366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.406

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000679

AC:

AN:

147316

Hom.:

Cov.:

AF XY:

0.0000697

AC XY:

AN XY:

71718

show subpopulations

African (AFR)

AF:

0.000175

AC:

AN:

39890

American (AMR)

AF:

0.00

AC:

AN:

14892

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3396

East Asian (EAS)

AF:

0.000199

AC:

AN:

5022

South Asian (SAS)

AF:

0.000218

AC:

AN:

4586

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9900

Middle Eastern (MID)

AF:

0.00

AC:

AN:

302

European-Non Finnish (NFE)

AF:

0.0000151

AC:

AN:

66418

Other (OTH)

AF:

0.00

AC:

AN:

2006

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Publications

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10-93702522-ACCGCCGCCGCCGCCGCCG-ACCGCCGCCGCCGCCGCCGCCGCCGCCGCCG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over