Genetic Variant TMEM147:p.Glu70_Ala74del (chr19-35546664-ACCCGCAGGAGTTCATGAAGGCC-CT) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_StrongPM2

The NM_032635.4(TMEM147):c.208-8_222delACCCGCAGGAGTTCATGAAGGCCinsCT(p.Glu70_Ala74del) variant causes a splice acceptor, conservative inframe deletion, splice region, synonymous, intron change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

TMEM147
NM_032635.4 splice_acceptor, conservative_inframe_deletion, splice_region, synonymous, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.53

Variant links:

Genes affected

TMEM147 (HGNC:30414): (transmembrane protein 147) Enables ribosome binding activity. Located in endoplasmic reticulum membrane. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

TMEM147 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.20296296 fraction of the gene. Cryptic splice site detected, with MaxEntScore 3.6, offset of -18, new splice context is: tccccctgtgcttacttaAGcct. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM147	NM_032635.4 link	c.208-8_222delACCCGCAGGAGTTCATGAAGGCCinsCT	p.Glu70_Ala74del	splice_acceptor_variant, conservative_inframe_deletion, splice_region_variant, synonymous_variant, intron_variant	Exon 4 of 7	ENST00000222284.10	NP_116024.1	Q9BVK8-1
TMEM147	NM_001242597.2 link	c.61-8_75delACCCGCAGGAGTTCATGAAGGCCinsCT	p.Glu21_Ala25del	splice_acceptor_variant, conservative_inframe_deletion, splice_region_variant, synonymous_variant, intron_variant	Exon 3 of 6		NP_001229526.1	Q9BVK8-2
TMEM147	NM_001242598.2 link	c.207+79_207+101delACCCGCAGGAGTTCATGAAGGCCinsCT		intron_variant	Intron 3 of 4		NP_001229527.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM147	ENST00000222284.10 link	c.208-8_222delACCCGCAGGAGTTCATGAAGGCCinsCT	p.Glu70_Ala74del	splice_acceptor_variant, conservative_inframe_deletion, splice_region_variant, synonymous_variant, intron_variant	Exon 4 of 7	1	NM_032635.4	ENSP00000222284.4		Q9BVK8-1

Frequencies

GnomAD3 genomes

Cov.:

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.