rs766267043

Variant names:

• chr19-35545770-G-A
• rs766267043
• NM_032635.4:c.31G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-35545770-G-A
• chr19-35545770-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1 PM2

The NM_032635.4(TMEM147):​c.31G>A​(p.Ala11Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,102 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: TMEM147 NM_032635.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.59

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

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM1: In a chain BOS complex subunit TMEM147 (size 223) in uniprot entity TM147_HUMAN there are 6 pathogenic changes around while only 1 benign (86%) in NM_032635.4
• 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	c.31G>A	p.Ala11Thr	missense_variant	Exon 1 of 7	ENST00000222284.10	NP_116024.1
TMEM147	NM_001242598.2	c.31G>A	p.Ala11Thr	missense_variant	Exon 1 of 5		NP_001229527.1
TMEM147	NM_001242597.2	c.-188G>A		5_prime_UTR_variant	Exon 1 of 6		NP_001229526.1
TMEM147-AS1	NR_038396.1	n.93+167C>T		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM147	ENST00000222284.10	c.31G>A	p.Ala11Thr	missense_variant	Exon 1 of 7	1	NM_032635.4	ENSP00000222284.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461102 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 726910

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T;.
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D;D
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.59	D;D
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.9	M;.
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-3.0	D;D
REVEL	Uncertain	0.29
Sift	Benign	0.034	D;D
Sift4G	Uncertain	0.057	T;T
Polyphen		0.98	D;.
Vest4		0.53
MutPred		0.75		Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);
MVP		0.34
MPC		1.1
ClinPred		0.99	D
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.23
gMVP		0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs766267043; hg19: chr19-36036672;