10-93676664-T-C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_145246.5(FRA10AC1):c.815A>G(p.Asp272Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000212 in 1,413,720 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

FRA10AC1
NM_145246.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.168

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: G2P, Ambry Genetics

FRA10AC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.053726405).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRA10AC1	NM_145246.5 link	c.815A>G	p.Asp272Gly	missense_variant	Exon 12 of 14	ENST00000359204.5	NP_660289.2	Q70Z53-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRA10AC1	ENST00000359204.5 link	c.815A>G	p.Asp272Gly	missense_variant	Exon 12 of 14	1	NM_145246.5	ENSP00000360488.3		Q70Z53-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000474

AC:

AN:

211016

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000994

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000212

AC:

AN:

1413720

Hom.:

Cov.:

AF XY:

0.00000285

AC XY:

AN XY:

701908

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31002

American (AMR)

AF:

0.00

AC:

AN:

33722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24360

East Asian (EAS)

AF:

0.00

AC:

AN:

37708

South Asian (SAS)

AF:

0.00

AC:

AN:

78144

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51946

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5612

European-Non Finnish (NFE)

AF:

0.00000274

AC:

AN:

1093144

Other (OTH)

AF:

0.00

AC:

AN:

58082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000825

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Jan 18, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.815A>G (p.D272G) alteration is located in exon 12 (coding exon 11) of the FRA10AC1 gene. This alteration results from a A to G substitution at nucleotide position 815, causing the aspartic acid (D) at amino acid position 272 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.0058

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.57

M_CAP

Benign

0.0069

MetaRNN

Benign

0.054

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PhyloP100

-0.17

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.4

REVEL

Benign

0.048

Sift

Benign

0.16

Sift4G

Benign

0.12

Polyphen

0.0

Vest4

0.079

MutPred

0.18

Loss of helix (P = 0.0123);

MVP

0.27

MPC

0.077

ClinPred

0.054

GERP RS

-0.10

Varity_R

0.039

gMVP

0.16

Mutation Taster

=70/30

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over