19-35546537-G-A

Variant names:

• chr19-35546537-G-A
• rs746637173
• NM_032635.4:c.159G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_032635.4(TMEM147):​c.159G>A​(p.Leu53Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TMEM147 NM_032635.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0960
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with facial dysmorphism, absent language, and pseudo-pelger-huet anomaly

  Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia
• complex neurodevelopmental disorder

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP7: Synonymous conserved (PhyloP=-0.096 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032635.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM147	NM_032635.4	MANE Select	c.159G>A	p.Leu53Leu	synonymous	Exon 3 of 7	NP_116024.1	Q9BVK8-1
	TMEM147	NM_001242597.2		c.12G>A	p.Leu4Leu	synonymous	Exon 2 of 6	NP_001229526.1	Q9BVK8-2
	TMEM147	NM_001242598.2		c.159G>A	p.Leu53Leu	synonymous	Exon 3 of 5	NP_001229527.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM147	ENST00000222284.10	TSL:1 MANE Select	c.159G>A	p.Leu53Leu	synonymous	Exon 3 of 7	ENSP00000222284.4	Q9BVK8-1
	TMEM147	ENST00000928931.1		c.159G>A	p.Leu53Leu	synonymous	Exon 3 of 7	ENSP00000598990.1
	TMEM147	ENST00000928929.1		c.159G>A	p.Leu53Leu	synonymous	Exon 3 of 7	ENSP00000598988.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_noAF	Benign	-0.63
CADD	Benign	11
DANN	Benign	0.82
PhyloP100		-0.096

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs746637173; hg19: chr19-36037439;