chr19-35545746-C-T

Variant names:

• chr19-35545746-C-T
• NM_032635.4:c.7C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001242597.2(TMEM147):​c.-212C>T variant causes a 5 prime UTR premature start codon gain 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TMEM147 NM_001242597.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.487
• 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-AS1 (HGNC:51273): (TMEM147 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 19-35545746-C-T is Benign according to our data. Variant chr19-35545746-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2571039.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001242597.2. 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.7C>T	p.Leu3Leu	synonymous	Exon 1 of 7	NP_116024.1	Q9BVK8-1
	TMEM147	NM_001242597.2		c.-212C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	NP_001229526.1	Q9BVK8-2
	TMEM147	NM_001242598.2		c.7C>T	p.Leu3Leu	synonymous	Exon 1 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.7C>T	p.Leu3Leu	synonymous	Exon 1 of 7	ENSP00000222284.4	Q9BVK8-1
	TMEM147-AS1	ENST00000589137.5	TSL:1	n.93+191G>A		intron	N/A
	TMEM147	ENST00000392204.6	TSL:2	c.-212C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	ENSP00000376040.1	Q9BVK8-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	12
DANN	Benign	0.89
PhyloP100		0.49
PromoterAI		0.11	Neutral

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

Other links and lift over

hg19: chr19-36036648;