FAM177A1

protein-coding

family with sequence similarity 177 member A1

Gene summary

This gene encodes a member of a conserved protein family. Alternative splicing results in multiple transcript variants. This gene is thought to be associated with susceptibility to juvenile idiopathic arthritis. [provided by RefSeq, Apr 2017]

Previous symbols:

C14orf24

MANE transcript

NM_173607.5

Inheritance

ClinVar variants

P:7U:47B:5

Top phenotype

Mendelian neurodevelopmental disorder

gnomAD constraint

pLI —, LoF o/e 0.58

Max pathogenic AF

—

Genomic locus

chr14:35,045,117-35,116,630

External References & Databases

Ensembl (ENSG00000151327)

Transcript & Mutation Effects

hg38 • Region Span ~71.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

complex neurodevelopmental disorderMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0100038

Submitter: Ambry Genetics

Mendelian neurodevelopmental disorderSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0100500

Submitter: PanelApp Australia

complex neurodevelopmental disorderMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0100038

Submitter: G2P

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FAM177A1 variants in ClinVar

8 Conditions Cataloged

not specifiedTotal: 41

not providedTotal: 6

FAM177A1-related disorderTotal: 2

Neurodevelopmental disorder with white matter abnormalities and gait disturbanceTotal: 2

Mild obesityTotal: 1

Intellectual disabilityTotal: 1

DolichocephalyTotal: 1

MacrocephalyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_173607.5. 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	3 clinvar		4
missense			41 clinvar	2 clinvar		43
nonsense	1 clinvar					1
start loss		1 clinvar				1
frameshift	2 clinvar	1 clinvar				3
splice donor/acceptor (+/-2bp)		2 clinvar	5 clinvar			7
Total	3	4	47	5	0	59

Highest pathogenic variant AF is 0.000008054493

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 38 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_173607.5	RefSeq	NP_775878.2	5	MANE Select
ENST00000280987.9	Ensembl	ENSP00000280987.4	5	MANE Select
NM_001079519.1	RefSeq	NP_001072987.1	5	Standard
NM_001289022.3	RefSeq	NP_001275951.1	5	Standard

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000280987
Coding exons: 5
Length: 68224
Individuals with no LoFs: 125727
Homozygous LoFs: 0
Heterozygous LoFs: 21
Defined: 125748
p: 0.0000835

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.302	131	122	1.08	0.00000573	1532
Missense (PolyPhen)		44	46.966	0.93685		604
Synonymous	-0.803	48	41.4	1.16	0.00000195	436
Loss of Function	1.26	6	10.4	0.577	4.46e-7	140

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00038	0.00038	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000035	0.000035	rare
South Asian	0.000098	0.000098	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.0945

Intolerance Scores

LoFtool: 0.231
RVIS EVS: 0.13
RVIS percentile EVS: 63

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.221

Gene Damage Prediction

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