NM_178545.4:c.565A>G

Variant names:

• chr1-1917947-T-C
• rs746833826
• NM_178545.4:c.565A>G

Variant summary

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

The NM_178545.4(TMEM52):​c.565A>G​(p.Thr189Ala) variant causes a missense 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TMEM52 NM_178545.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.777
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04001674).

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.565A>G	p.Thr189Ala	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.565A>G	p.Thr189Ala	missense	Exon 5 of 5	ENSP00000311122.3	Q8NDY8-1
	TMEM52	ENST00000378602.3	TSL:1	c.520A>G	p.Thr174Ala	missense	Exon 2 of 2	ENSP00000367865.3	Q8NDY8-2
	TMEM52	ENST00000902364.1		c.583A>G	p.Thr195Ala	missense	Exon 5 of 5	ENSP00000572423.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	2.3
DANN	Benign	0.56
DEOGEN2	Benign	0.0016	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.78
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.95	N
REVEL	Benign	0.024
Sift	Benign	0.16	T
Sift4G	Benign	0.75	T
Polyphen		0.0020	B
Vest4		0.12
MutPred		0.13		Loss of glycosylation at T189 (P = 6e-04)
MVP		0.061
MPC		0.042
ClinPred		0.11	T
GERP RS		-5.0
Varity_R		0.053
gMVP		0.21
Mutation Taster		=99/1	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: rs746833826; hg19: chr1-1849386;