FRA10AC1

protein-coding

FRA10A associated CGG repeat 1, the group of Spliceosomal C complex

Gene summary

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]

Previous symbols:

C10orf4

MANE transcript

NM_145246.5

Inheritance

ClinVar variants

P:11U:52B:4

Top phenotype

Neurodevelopmental disorder with growth retardation, dysmorphic facies, and corpus callosum abnormalitie

gnomAD constraint

pLI —, LoF o/e 0.78

Max pathogenic AF

—

Genomic locus

chr10:93,667,883-93,702,592

External References & Databases

Ensembl (ENSG00000148690)

Transcript & Mutation Effects

hg38 • Region Span ~34.7 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorder with growth retardation, dysmorphic facies, and corpus callosum abnormalitiesSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0859312

Submitter: G2P

neurodevelopmental disorder with growth retardation, dysmorphic facies, and corpus callosum abnormalitiesSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0859312

Submitter: PanelApp Australia

neurodevelopmental disorder with growth retardation, dysmorphic facies, and corpus callosum abnormalitiesMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0859312

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Neurodevelopmental disorder with growth retardation, dysmorphic facies, and corpus callosum abnormalitieAR

Manifestation: Craniofacial; Musculoskeletal; Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 34694367; 35821753; 35871492

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FRA10AC1 variants in ClinVar

6 Conditions Cataloged

Inborn genetic diseasesTotal: 37

not providedTotal: 12

Neurodevelopmental disorder with growth retardation, dysmorphic facies, and corpus callosum abnormalitiesTotal: 12

See casesTotal: 2

not specifiedTotal: 1

FRA10AC1-related conditionTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_145246.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	1 clinvar		2
missense			40 clinvar	3 clinvar		43
nonsense	2 clinvar	2 clinvar	1 clinvar			5
start loss	1 clinvar					1
frameshift	2 clinvar	1 clinvar	1 clinvar			4
splice donor/acceptor (+/-2bp)	1 clinvar	2 clinvar	9 clinvar			12
Total	6	5	52	4	0	67

Highest pathogenic variant AF is 0.000068434536

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 69 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_145246.5	RefSeq	NP_660289.2	13	MANE Select
ENST00000359204.5	Ensembl	ENSP00000360488.3	13	MANE Select
NM_001347712.2	RefSeq	NP_001334641.1	13	Standard
NM_001347713.2	RefSeq	NP_001334642.1	13	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Molecular Function

protein binding

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000359204
Coding exons: 13
Length: 34690
Individuals with no LoFs: 125684
Homozygous LoFs: 0
Heterozygous LoFs: 56
Defined: 125740
p: 0.000223

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.475	128	144	0.889	0.00000659	2084
Missense (PolyPhen)		35	45.496	0.76929		656
Synonymous	2.68	24	47.4	0.506	0.00000222	464
Loss of Function	0.962	17	21.9	0.778	0.00000102	320

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00047	0.00043	rare
Latino/Admixed American	0.00021	0.00017	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00064	0.00060	rare
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.00020	0.00019	rare
South Asian	0.00032	0.00029	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.0830

Intolerance Scores

RVIS EVS: 0.75
RVIS percentile EVS: 86.57

Essentials

Essential (CRISPR): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.731

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	High