12-66137019-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016056.4(TMBIM4):c.*941G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.781 in 152,200 control chromosomes in the GnomAD database, including 47,450 homozygotes. 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: 𝑓 0.78 (47450 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: TMBIM4 NM_016056.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.794

Genes affected

TMBIM4 (HGNC:24257): (transmembrane BAX inhibitor motif containing 4) Involved in negative regulation of apoptotic process and regulation of calcium-mediated signaling. Located in Golgi stack. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.93 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMBIM4	NM_016056.4	c.*941G>C		3_prime_UTR_variant	7/7	ENST00000358230.8
TMBIM4	NM_001282606.2	c.*941G>C		3_prime_UTR_variant	8/8
TMBIM4	NM_001282609.2	c.*1134G>C		3_prime_UTR_variant	7/7
TMBIM4	NM_001282610.2	c.*941G>C		3_prime_UTR_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMBIM4	ENST00000358230.8	c.*941G>C		3_prime_UTR_variant	7/7	1	NM_016056.4	P1
TMBIM4	ENST00000544599.5	c.*941G>C		3_prime_UTR_variant	7/7	1

Frequencies

GnomAD3 genomes AF: 0.781 AC: 118776 AN: 152082 Hom.: 47400 Cov.: 33

Gnomad AFR AF: 0.938

Gnomad AMI AF: 0.811

Gnomad AMR AF: 0.621

Gnomad ASJ AF: 0.813

Gnomad EAS AF: 0.880

Gnomad SAS AF: 0.756

Gnomad FIN AF: 0.710

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.725

Gnomad OTH AF: 0.752

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.781 AC: 118882 AN: 152200 Hom.: 47450 Cov.: 33 AF XY: 0.779 AC XY: 57981 AN XY: 74394

Gnomad4 AFR AF: 0.938

Gnomad4 AMR AF: 0.621

Gnomad4 ASJ AF: 0.813

Gnomad4 EAS AF: 0.880

Gnomad4 SAS AF: 0.756

Gnomad4 FIN AF: 0.710

Gnomad4 NFE AF: 0.725

Gnomad4 OTH AF: 0.749

Alfa AF: 0.732 Hom.: 4884

Bravo AF: 0.778

Asia WGS AF: 0.807 AC: 2805 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.6
Dann	Benign	0.59

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

LitVar

Other links and lift over

dbSNP: rs1168754; hg19: chr12-66530799;