TMEM147

transmembrane protein 147

Basic information

Region (hg38): 19:35545600-35547526

Links

ENSG00000105677 ∙ NCBI:10430 ∙ OMIM:613585 ∙ HGNC:30414 ∙ Uniprot:Q9BVK8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• complex neurodevelopmental disorder (Moderate), mode of inheritance: AR
• neurodevelopmental disorder with facial dysmorphism, absent language, and pseudo-pelger-huet anomaly (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with facial dysmorphism, absent language, and pseudo-Pelger-Huet anomaly	AR	General	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	Craniofacial; Hematologic; Musculoskeletal; Neurologic	36044892

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TMEM147 gene.

• Neurodevelopmental disorder with facial dysmorphism, absent language, and pseudo-pelger-huet anomaly (11 variants)
• Poor speech;Intellectual disability, severe;Abnormal facial shape;Absent speech;Motor delay (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TMEM147 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				2		2
missense	2		15			17
nonsense	3		1			4
start loss						0
frameshift	4					4
inframe indel						0
splice donor/acceptor (+/-2bp)	1		1			2
splice region	1			1		2
non coding					1	1
Total	10	0	17	2	1

Highest pathogenic variant AF is 0.0000329

Variants in TMEM147

This is a list of pathogenic ClinVar variants found in the TMEM147 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
19-35545745-C-T			Likely benign (May 01, 2023)
19-35545746-C-T			Likely benign (May 01, 2023)
19-35545753-A-C			Uncertain significance (Jan 04, 2023)
19-35545758-G-C		Neurodevelopmental disorder with facial dysmorphism, absent language, and pseudo-pelger-huet anomaly • Inborn genetic diseases	Conflicting classifications of pathogenicity (Oct 19, 2023)
19-35545770-G-C		Neurodevelopmental disorder with facial dysmorphism, absent language, and pseudo-pelger-huet anomaly	Uncertain significance (Mar 23, 2023)
19-35545773-C-T		Inborn genetic diseases	Uncertain significance (Jan 16, 2024)
19-35545802-C-G		Neurodevelopmental disorder with facial dysmorphism, absent language, and pseudo-pelger-huet anomaly	Pathogenic (Oct 28, 2022)
19-35545902-C-T		Inborn genetic diseases	Uncertain significance (Jan 04, 2024)
19-35545908-GGAAATGCGTCCAGGCTGGA-G		Neurodevelopmental disorder with facial dysmorphism, absent language, and pseudo-pelger-huet anomaly	Pathogenic (-)
19-35545947-A-C		Neurodevelopmental disorder with facial dysmorphism, absent language, and pseudo-pelger-huet anomaly	Uncertain significance (Mar 23, 2023)
19-35546524-A-G		Inborn genetic diseases	Uncertain significance (Oct 19, 2023)
19-35546539-CCACTTTCTTT-C		Neurodevelopmental disorder with facial dysmorphism, absent language, and pseudo-pelger-huet anomaly	Pathogenic (-)
19-35546541-ACTTT-A		Neurodevelopmental disorder with facial dysmorphism, absent language, and pseudo-pelger-huet anomaly	Pathogenic (Oct 18, 2022)
19-35546581-T-C		Inborn genetic diseases	Uncertain significance (Nov 30, 2022)
19-35546711-G-C		Inborn genetic diseases	Uncertain significance (Oct 05, 2023)
19-35546759-A-C		Inborn genetic diseases	Uncertain significance (May 26, 2024)
19-35546786-A-G		Inborn genetic diseases	Uncertain significance (Nov 14, 2023)
19-35546813-G-A		Motor delay;Poor speech;Intellectual disability, severe;Abnormal facial shape;Absent speech • Neurodevelopmental disorder with facial dysmorphism, absent language, and pseudo-pelger-huet anomaly	Pathogenic (-)
19-35546818-G-A		TMEM147-related disorder	Benign (Jul 08, 2019)
19-35546944-G-T		Neurodevelopmental disorder with facial dysmorphism, absent language, and pseudo-pelger-huet anomaly	Pathogenic (Feb 23, 2023)
19-35546970-C-T		Inborn genetic diseases	Uncertain significance (Jun 21, 2021)
19-35546990-G-A		Neurodevelopmental disorder with facial dysmorphism, absent language, and pseudo-pelger-huet anomaly	Pathogenic (-)
19-35546998-T-A		Neurodevelopmental disorder with facial dysmorphism, absent language, and pseudo-pelger-huet anomaly	Pathogenic (Oct 28, 2022)
19-35547017-C-CA		Neurodevelopmental disorder with facial dysmorphism, absent language, and pseudo-pelger-huet anomaly	Pathogenic (Oct 28, 2022)
19-35547019-A-G		Inborn genetic diseases	Uncertain significance (Jul 06, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TMEM147	protein_coding	protein_coding	ENST00000222284	7	1932

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000140	0.870	125724	0	24	125748	0.0000954

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.485	121	137	0.883	0.00000796	1465
Missense in Polyphen		37	50.098	0.73855		568
Synonymous	0.325	51	54.0	0.944	0.00000328	440
Loss of Function	1.38	8	13.5	0.594	6.61e-7	141

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000154	0.000152
Ashkenazi Jewish	0.00	0.00
East Asian	0.000217	0.000217
Finnish	0.00	0.00
European (Non-Finnish)	0.0000796	0.0000791
Middle Eastern	0.000217	0.000217
South Asian	0.000229	0.000229
Other	0.000165	0.000163

dbNSFP

Source: dbNSFP

Recessive Scores

• pRec: 0.140

Intolerance Scores

• loftool: 0.676
• rvis_EVS: -0.3
• rvis_percentile_EVS: 32.62

Haploinsufficiency Scores

• pHI: 0.194
• hipred: N
• hipred_score: 0.429
• ghis: 0.603

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.653

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tmem147

Gene ontology

• Cellular component: endoplasmic reticulum membrane;integral component of membrane;protein-containing complex
• Molecular function: protein binding