SCNM1

protein-coding

sodium channel modifier 1

Gene summary

SCNM1 is a zinc finger protein and putative splicing factor. In mice, Scnm1 modifies phenotypic expression of Scn8a (MIM 600702) mutations (Buchner et al., 2003 [PubMed 12920299]).[supplied by OMIM, Oct 2009]

MANE transcript

NM_024041.4

Inheritance

ClinVar variants

P:4U:34B:3

Top phenotype

Orofaciodigital syndrome XIX

gnomAD constraint

pLI —, LoF o/e 0.66

Max pathogenic AF

—

Genomic locus

chr1:151,156,664-151,170,296

External References & Databases

Ensembl (ENSG00000163156)

Transcript & Mutation Effects

hg38 • Region Span ~13.6 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

orofaciodigital syndrome 19LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0859310

Submitter: Ambry Genetics

orofaciodigital syndrome 19LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0859310

Submitter: G2P

orofaciodigital syndrome 19STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0859310

Submitter: Labcorp Genetics (formerly Invitae)

orofaciodigital syndrome 19STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0859310

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Orofaciodigital syndrome XIXAR

Manifestation: Craniofacial; Dental; 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: 36084634

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SCNM1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 33

not providedTotal: 5

Orofaciodigital syndrome 19Total: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_024041.4. 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			1 clinvar	1 clinvar		2
missense	1 clinvar		33 clinvar	2 clinvar		36
nonsense						0
start loss						0
frameshift	1 clinvar	1 clinvar				2
splice donor/acceptor (+/-2bp)	1 clinvar					1
Total	3	1	34	3	0	41

Highest pathogenic variant AF is 0.000005576077

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 37 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_024041.4	RefSeq	NP_076946.1	7	MANE Select
ENST00000368905.9	Ensembl	ENSP00000357901.4	7	MANE Select
NM_001204856.2	RefSeq	NP_001191785.1	6	Standard
ENST00000368902.1	Ensembl	ENSP00000357898.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

alternative mRNA splicing, via spliceosome
RNA splicing

Molecular Function

protein binding
enzyme binding
metal ion binding

Cellular Component

nucleus
nuclear speck

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000368905
Coding exons: 7
Length: 13634
Individuals with no LoFs: 125703
Homozygous LoFs: 0
Heterozygous LoFs: 44
Defined: 125747
p: 0.000175

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.135	124	128	0.966	0.00000674	1474
Missense (PolyPhen)		61	62.036	0.9833		677
Synonymous	0.117	46	47.0	0.978	0.00000239	458
Loss of Function	1.28	11	16.6	0.661	0.00000120	156

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00062	0.00062	rare
Latino/Admixed American	0.00014	0.00014	rare
Ashkenazi Jewish	0.00089	0.00089	rare
East Asian	0.00033	0.00033	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000080	0.000079	rare
South Asian	0.00013	0.00013	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays a role in RNA splicing, possibly contributing to the recognition of non-consensus donor sites. {ECO:0000250}.;

Recessive Scores

pRec: 0.113

Intolerance Scores

LoFtool: 0.496
RVIS EVS: 0.35
RVIS percentile EVS: 74.18

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.907

Gene Damage Prediction

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