Genetic Variant FRA10AC1:c.-166_-149dupCGGCGGCGGCGGCGGCGG (chr10-93702522-A-ACCGCCGCCGCCGCCGCCG) – 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.-166_-149dupCGGCGGCGGCGGCGGCGG 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 0.000054 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000058 ( 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.-166_-149dupCGGCGGCGGCGGCGGCGG	5_prime_UTR	Exon 1 of 14	NP_660289.2
FRA10AC1	NM_001347712.2		c.-367_-350dupCGGCGGCGGCGGCGGCGG	5_prime_UTR	Exon 1 of 14	NP_001334641.1	Q70Z53-1
FRA10AC1	NM_001347713.2		c.-286_-269dupCGGCGGCGGCGGCGGCGG	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.-166_-149dupCGGCGGCGGCGGCGGCGG	5_prime_UTR	Exon 1 of 14	ENSP00000360488.3	Q70Z53-1
FRA10AC1	ENST00000959343.1		c.-166_-149dupCGGCGGCGGCGGCGGCGG	5_prime_UTR	Exon 1 of 14	ENSP00000629402.1
FRA10AC1	ENST00000905754.1		c.-367_-350dupCGGCGGCGGCGGCGGCGG	5_prime_UTR	Exon 1 of 14	ENSP00000575813.1

Frequencies

GnomAD3 genomes

AF:

0.0000543

AC:

AN:

147320

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000100

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000201

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00331

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000583

AC:

AN:

68614

Hom.:

Cov.:

AF XY:

0.0000233

AC XY:

AN XY:

42852

show subpopulations

African (AFR)

AF:

0.00295

AC:

AN:

1018

American (AMR)

AF:

0.00

AC:

AN:

2066

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

976

East Asian (EAS)

AF:

0.00

AC:

AN:

1206

South Asian (SAS)

AF:

0.00

AC:

AN:

12402

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2786

Middle Eastern (MID)

AF:

0.00

AC:

AN:

228

European-Non Finnish (NFE)

AF:

0.0000224

AC:

AN:

44564

Other (OTH)

AF:

0.00

AC:

AN:

3368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.725

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000543

AC:

AN:

147436

Hom.:

Cov.:

AF XY:

0.0000278

AC XY:

AN XY:

71844

show subpopulations

African (AFR)

AF:

0.000100

AC:

AN:

40006

American (AMR)

AF:

0.000201

AC:

AN:

14912

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3396

East Asian (EAS)

AF:

0.00

AC:

AN:

5010

South Asian (SAS)

AF:

0.00

AC:

AN:

4582

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9900

Middle Eastern (MID)

AF:

0.00352

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66414

Other (OTH)

AF:

0.00

AC:

AN:

2028

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

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

Mutation Taster

=300/0

polymorphism

(source)

Splicing

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

Publications

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10-93702522-ACCGCCGCCGCCGCCGCCG-ACCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCG

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