rs1168754

Positions:

• chr12-66137019-C-A
• chr12-66137019-C-G
• chr12-66137019-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016056.4(TMBIM4):​c.*941G>T variant causes a 3 prime UTR 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: 33)
• 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]

ENSG00000228144 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMBIM4	NM_016056.4	c.*941G>T		3_prime_UTR_variant	7/7	ENST00000358230.8	NP_057140.2
TMBIM4	NM_001282606.2	c.*941G>T		3_prime_UTR_variant	8/8		NP_001269535.1
TMBIM4	NM_001282610.2	c.*941G>T		3_prime_UTR_variant	7/7		NP_001269539.1
TMBIM4	NM_001282609.2	c.*1134G>T		3_prime_UTR_variant	7/7		NP_001269538.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMBIM4	ENST00000358230	c.*941G>T		3_prime_UTR_variant	7/7	1	NM_016056.4	ENSP00000350965.3
TMBIM4	ENST00000544599	c.*941G>T		3_prime_UTR_variant	7/7	1		ENSP00000444639.1
ENSG00000228144	ENST00000539652.1	n.*123+945G>T		intron_variant		2		ENSP00000454670.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.14

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;