rs745505195

Variant names:

• chr12-10189988-A-C
• rs745505195
• NM_001384896.1:c.400A>C

Your query was ambiguous. Multiple possible variants found:

• chr12-10189988-A-C
• chr12-10189988-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001384896.1(TMEM52B):​c.400A>C​(p.Thr134Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,613,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. T134S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: TMEM52B NM_001384896.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.25
• Publications: 1 publications found

Genes affected

TMEM52B (HGNC:26438): (transmembrane protein 52B) Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37135184).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384896.1. 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
	TMEM52B	NM_001384896.1	MANE Select	c.400A>C	p.Thr134Pro	missense	Exon 5 of 5	NP_001371825.1	Q4KMG9-1
	TMEM52B	NM_001079815.2		c.400A>C	p.Thr134Pro	missense	Exon 6 of 6	NP_001073283.1	Q4KMG9-1
	TMEM52B	NM_001384894.1		c.400A>C	p.Thr134Pro	missense	Exon 8 of 8	NP_001371823.1	Q4KMG9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM52B	ENST00000543484.2	TSL:4 MANE Select	c.400A>C	p.Thr134Pro	missense	Exon 5 of 5	ENSP00000445582.2	Q4KMG9-1
	TMEM52B	ENST00000298530.7	TSL:1	c.340A>C	p.Thr114Pro	missense	Exon 4 of 4	ENSP00000298530.3	Q4KMG9-2
	TMEM52B	ENST00000381923.6	TSL:5	c.400A>C	p.Thr134Pro	missense	Exon 6 of 6	ENSP00000371348.2	Q4KMG9-1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151952 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461882 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727238

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: 39698

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

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

European-Non Finnish (NFE) AF: 0.00000809 AC: 9 AN: 1112006

Other (OTH) AF: 0.0000166 AC: 1 AN: 60394

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151952 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74222

African (AFR) AF: 0.00 AC: 0 AN: 41372

American (AMR) AF: 0.00 AC: 0 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67992

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.010	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.017	T
Eigen	Benign	0.12
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		3.3
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.59	N
REVEL	Benign	0.11
Sift	Benign	0.14	T
Sift4G	Benign	0.20	T
Polyphen		0.90	P
Vest4		0.49
MutPred		0.24		Loss of helix (P = 0.028)
MVP		0.36
MPC		0.43
ClinPred		0.76	D
GERP RS		2.3
Varity_R		0.17
gMVP		0.33
Mutation Taster		=86/14	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: rs745505195; hg19: chr12-10342587;