12-125326510-A-T

Variant names:

• chr12-125326510-A-T
• rs550677
• NM_001366854.1:c.68-22942A>T

Variant summary

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

The NM_001366854.1(TMEM132B):​c.68-22942A>T variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.3e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TMEM132B NM_001366854.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.164
• Publications: 12 publications found

Genes affected

TMEM132B (HGNC:29397): (transmembrane protein 132B) 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 (BayesDel_noAF=-0.84).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366854.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM132B	NM_001366854.1	MANE Select	c.68-22942A>T		intron	N/A	NP_001353783.1
	TMEM132B	NM_052907.3		c.-114A>T		upstream_gene	N/A	NP_443139.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM132B	ENST00000682704.1	MANE Select	c.68-22942A>T		intron	N/A	ENSP00000507790.1
	TMEM132B	ENST00000299308.7	TSL:5	c.-114A>T		upstream_gene	N/A	ENSP00000299308.3
	TMEM132B	ENST00000535330.1	TSL:4	n.-41A>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 9.34e-7 AC: 1 AN: 1070966 Hom.: 0 Cov.: 14 AF XY: 0.00 AC XY: 0 AN XY: 542642

African (AFR) AF: 0.00 AC: 0 AN: 25538

American (AMR) AF: 0.00 AC: 0 AN: 35072

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23006

East Asian (EAS) AF: 0.00 AC: 0 AN: 34460

South Asian (SAS) AF: 0.00 AC: 0 AN: 72242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44962

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5014

European-Non Finnish (NFE) AF: 0.00000128 AC: 1 AN: 783616

Other (OTH) AF: 0.00 AC: 0 AN: 47056

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	11
DANN	Benign	0.66
PhyloP100		0.16
PromoterAI		0.026	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs550677; hg19: chr12-125811056;