chr12-10179600-C-T

Variant names:

• chr12-10179600-C-T
• rs768022750
• NM_001384896.1:c.26C>T

Variant summary

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

The NM_001384896.1(TMEM52B):​c.26C>T​(p.Ala9Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000958 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 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. A9G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: TMEM52B NM_001384896.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.617
• Publications: 2 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: 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=0.048439533).

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.26C>T	p.Ala9Val	missense	Exon 1 of 5	NP_001371825.1	Q4KMG9-1
	TMEM52B	NM_001079815.2		c.26C>T	p.Ala9Val	missense	Exon 2 of 6	NP_001073283.1	Q4KMG9-1
	TMEM52B	NM_001384894.1		c.26C>T	p.Ala9Val	missense	Exon 4 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.26C>T	p.Ala9Val	missense	Exon 1 of 5	ENSP00000445582.2	Q4KMG9-1
	TMEM52B	ENST00000298530.7	TSL:1	c.10C>T	p.Arg4Trp	missense	Exon 1 of 4	ENSP00000298530.3	Q4KMG9-2
	TMEM52B	ENST00000381923.6	TSL:5	c.26C>T	p.Ala9Val	missense	Exon 2 of 6	ENSP00000371348.2	Q4KMG9-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000239 AC: 6 AN: 251478 AF XY: 0.0000294

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000958 AC: 14 AN: 1461876 Hom.: 0 Cov.: 30 AF XY: 0.0000110 AC XY: 8 AN XY: 727242

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: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000116 AC: 10 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: 0.00000180 AC: 2 AN: 1112000

Other (OTH) AF: 0.0000331 AC: 2 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000330 AC: 4

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	1.3
DANN	Benign	0.60
DEOGEN2	Benign	0.0014	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-0.99	T
PhyloP100		-0.62
PROVEAN	Benign	0.0	N
REVEL	Benign	0.0080
Sift	Benign	0.72	T
Sift4G	Benign	0.38	T
Polyphen		0.0	B
Vest4		0.066
MutPred		0.31		Gain of catalytic residue at S11 (P = 0.0028)
MVP		0.040
ClinPred		0.017	T
GERP RS		-3.5
Varity_R		0.021
gMVP		0.35
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: rs768022750; hg19: chr12-10332199;