FAM50A

protein-coding

family with sequence similarity 50 member A, the group of MicroRNA protein coding host genes|Spliceosomal P complex|Spliceosomal C complex

Gene summary

This gene belongs to the FAM50 family. The encoded protein is highly conserved in length and sequence across different species. It is a basic protein containing a nuclear localization signal, and may function as a DNA-binding protein or a transcriptional factor. [provided by RefSeq, Sep 2009]

MANE transcript

NM_004699.4

Inheritance

ClinVar variants

P:5U:112B:15

Top phenotype

Intellectual disability disorder, X-linked, syndrome, Armfield type

gnomAD constraint

pLI —, LoF o/e 0.06

Max pathogenic AF

—

Genomic locus

chrX:154,444,141-154,450,654

External References & Databases

Ensembl (ENSG00000071859)

Transcript & Mutation Effects

hg38 • Region Span ~6.5 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Armfield syndromeSTRONG

Inheritance Pattern: XL

Disease ID:MONDO:0010284

Submitter: PanelApp Australia

Armfield syndromeMODERATE

Inheritance Pattern: XL

Disease ID:MONDO:0010284

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Intellectual disability disorder, X-linked, syndrome, Armfield typeXL

Manifestation: Craniofacial; Dental; Dermatologic; 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: 10398235; 32703943

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FAM50A variants in ClinVar

6 Conditions Cataloged

not providedTotal: 49

Inborn genetic diseasesTotal: 18

Armfield syndromeTotal: 10

not specifiedTotal: 8

FAM50A-related disorderTotal: 7

Intellectual disabilityTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004699.4. 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			9 clinvar	11 clinvar	1 clinvar	21
missense		5 clinvar	75 clinvar	3 clinvar		83
nonsense			4 clinvar			4
start loss			1 clinvar			1
frameshift						0
splice donor/acceptor (+/-2bp)			23 clinvar			23
Total	0	5	112	14	1	132

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 34 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004699.4	RefSeq	NP_004690.1	13	MANE Select
ENST00000393600.8	Ensembl	ENSP00000377225.3	13	MANE Select
ENST00000158526.9	Ensembl	ENSP00000158526.9	10	Standard
ENST00000854482.1	Ensembl	ENSP00000524541.1	13	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

spermatogenesis

Molecular Function

RNA binding

Cellular Component

nucleus
nucleoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000393600
Coding exons: 13
Length: 6530
Individuals with no LoFs: 125736
Homozygous LoFs: 1
Heterozygous LoFs: 1
Defined: 125738
p: 0.00000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.02	44	147	0.299	0.0000128	2278
Missense (PolyPhen)		10	56.655	0.17651		781
Synonymous	0.266	54	56.5	0.955	0.00000511	569
Loss of Function	3.51	1	16.3	0.0615	0.00000123	278

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000036	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000012	0.0000088	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May be a DNA-binding protein or transcriptional factor. {ECO:0000269|PubMed:9339379}.;

Recessive Scores

pRec: 0.141

Intolerance Scores

LoFtool: 0.171
RVIS EVS: -0.01
RVIS percentile EVS: 53.19

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: N
Indispensability score: 0.307

Gene Damage Prediction

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