19-35547017-C-CA

Position:

• chr19-35547017-C-CA

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_032635.4(TMEM147):​c.419dup​(p.Asn140LysfsTer21) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TMEM147 NM_032635.4 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 8.13

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]

ACMG classification

Verdict is Pathogenic. Variant got 12 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 19-35547017-C-CA is Pathogenic according to our data. Variant chr19-35547017-C-CA is described in ClinVar as [Pathogenic]. Clinvar id is 1708020.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM147	NM_032635.4	c.419dup	p.Asn140LysfsTer21	frameshift_variant	5/7	ENST00000222284.10
TMEM147	NM_001242597.2	c.272dup	p.Asn91LysfsTer21	frameshift_variant	4/6
TMEM147	NM_001242598.2	c.208-100dup		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM147	ENST00000222284.10	c.419dup	p.Asn140LysfsTer21	frameshift_variant	5/7	1	NM_032635.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Neurodevelopmental disorder with facial dysmorphism, absent language, and pseudo-pelger-huet anomaly Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Equipe Genetique des Anomalies du Developpement, Université de Bourgogne

Oct 28, 2022

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Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-36037919;