12-66137019-C-A

Variant names:

• chr12-66137019-C-A
• rs1168754
• NM_016056.4:c.*941G>T

Variant summary

Our verdict is Likely benign. The variant received -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
• Publications: 5 publications found

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

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=-0.91).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016056.4. 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
	TMBIM4	NM_016056.4	MANE Select	c.*941G>T		3_prime_UTR	Exon 7 of 7	NP_057140.2
	TMBIM4	NM_001282606.2		c.*941G>T		3_prime_UTR	Exon 8 of 8	NP_001269535.1
	TMBIM4	NM_001282610.2		c.*941G>T		3_prime_UTR	Exon 7 of 7	NP_001269539.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMBIM4	ENST00000358230.8	TSL:1 MANE Select	c.*941G>T		3_prime_UTR	Exon 7 of 7	ENSP00000350965.3
	TMBIM4	ENST00000544599.5	TSL:1	c.*941G>T		3_prime_UTR	Exon 7 of 7	ENSP00000444639.1
	ENSG00000228144	ENST00000539652.1	TSL:2	n.*123+945G>T		intron	N/A	ENSP00000454670.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.14
PhyloP100		-0.79

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: rs1168754; hg19: chr12-66530799;