1-1918005-T-A

Variant names:

• chr1-1918005-T-A
• rs766453845
• NM_178545.4:c.507A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_178545.4(TMEM52):​c.507A>T​(p.Glu169Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,676 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TMEM52 NM_178545.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.636
• Publications: 0 publications found

Genes affected

TMEM52 (HGNC:27916): (transmembrane protein 52) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08341703).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178545.4. 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
	TMEM52	NM_178545.4	MANE Select	c.507A>T	p.Glu169Asp	missense	Exon 5 of 5	NP_848640.1	Q8NDY8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM52	ENST00000310991.8	TSL:1 MANE Select	c.507A>T	p.Glu169Asp	missense	Exon 5 of 5	ENSP00000311122.3	Q8NDY8-1
	TMEM52	ENST00000378602.3	TSL:1	c.462A>T	p.Glu154Asp	missense	Exon 2 of 2	ENSP00000367865.3	Q8NDY8-2
	TMEM52	ENST00000902364.1		c.525A>T	p.Glu175Asp	missense	Exon 5 of 5	ENSP00000572423.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461676 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727118

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53220

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111998

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	15
DANN	Uncertain	1.0
DEOGEN2	Benign	0.033	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.077	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.083	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		-0.64
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.11
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.048	D
Polyphen		0.99	D
Vest4		0.081
MutPred		0.051		Loss of methylation at K165 (P = 0.1081)
MVP		0.085
MPC		0.28
ClinPred		0.92	D
GERP RS		0.15
Varity_R		0.55
gMVP		0.18
Mutation Taster		=95/5	polymorphism

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

dbSNP: rs766453845; hg19: chr1-1849444;