12-10190130-C-A

Variant names:

• chr12-10190130-C-A
• NM_001384896.1:c.542C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001384896.1(TMEM52B):​c.542C>A​(p.Ser181Tyr) 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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMEM52B NM_001384896.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.35

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09196538).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM52B	NM_001384896.1	c.542C>A	p.Ser181Tyr	missense_variant	Exon 5 of 5	ENST00000543484.2	NP_001371825.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM52B	ENST00000543484.2	c.542C>A	p.Ser181Tyr	missense_variant	Exon 5 of 5	4	NM_001384896.1	ENSP00000445582.2
TMEM52B	ENST00000298530.7	c.482C>A	p.Ser161Tyr	missense_variant	Exon 4 of 4	1		ENSP00000298530.3
TMEM52B	ENST00000381923.6	c.542C>A	p.Ser181Tyr	missense_variant	Exon 6 of 6	5		ENSP00000371348.2
TMEM52B	ENST00000546153.1	n.428C>A		non_coding_transcript_exon_variant	Exon 2 of 2	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 14, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.482C>A (p.S161Y) alteration is located in exon 4 (coding exon 4) of the TMEM52B gene. This alteration results from a C to A substitution at nucleotide position 482, causing the serine (S) at amino acid position 161 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	17
DANN	Benign	0.93
DEOGEN2	Benign	0.022	T;.
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.37	T;T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.092	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;.
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.77	N;N
REVEL	Benign	0.048
Sift	Uncertain	0.021	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.68	P;B
Vest4		0.093
MutPred		0.28		Gain of sheet (P = 0.0477);.;
MVP		0.10
MPC		0.25
ClinPred		0.22	T
GERP RS		3.1
Varity_R		0.070
gMVP		0.20

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-10342729;