2-218282159-G-C

Position:

• chr2-218282159-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_022152.6(TMBIM1):​c.-18C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 1,460,798 control chromosomes in the GnomAD database, including 110,223 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 0.34 (9547 hom., cov: 33)
  • Exomes 𝑓: 0.39 (100676 hom.)
• Consequence: TMBIM1 NM_022152.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.55

Genes affected

TMBIM1 (HGNC:23410): (transmembrane BAX inhibitor motif containing 1) Enables death receptor binding activity. Involved in negative regulation of Fas signaling pathway; negative regulation of extrinsic apoptotic signaling pathway via death domain receptors; and negative regulation of protein localization to plasma membrane. Located in Golgi apparatus; endosome membrane; and lysosomal membrane. [provided by Alliance of Genome Resources, Apr 2022]

PNKD (HGNC:9153): (PNKD metallo-beta-lactamase domain containing) This gene is thought to play a role in the regulation of myofibrillogenesis. Mutations in this gene have been associated with the movement disorder paroxysmal non-kinesigenic dyskinesia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010]

TMBIM1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMBIM1	NM_022152.6	c.-18C>G		5_prime_UTR_variant	2/12	ENST00000258412.8	NP_071435.2
PNKD	NM_015488.5	c.236+10610G>C		intron_variant		ENST00000273077.9	NP_056303.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMBIM1	ENST00000258412.8	c.-18C>G		5_prime_UTR_variant	2/12	1	NM_022152.6	ENSP00000258412.3
PNKD	ENST00000273077.9	c.236+10610G>C		intron_variant		1	NM_015488.5	ENSP00000273077.4

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52175 AN: 151978 Hom.: 9549 Cov.: 33

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.426

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.404

Gnomad OTH AF: 0.382

GnomAD3 exomes AF: 0.341 AC: 38966 AN: 114400 Hom.: 6523 AF XY: 0.344 AC XY: 20956 AN XY: 60998

Gnomad AFR exome AF: 0.185

Gnomad AMR exome AF: 0.409

Gnomad ASJ exome AF: 0.343

Gnomad EAS exome AF: 0.348

Gnomad SAS exome AF: 0.307

Gnomad FIN exome AF: 0.285

Gnomad NFE exome AF: 0.370

Gnomad OTH exome AF: 0.351

GnomAD4 exome AF: 0.390 AC: 510466 AN: 1308702 Hom.: 100676 Cov.: 33 AF XY: 0.389 AC XY: 248144 AN XY: 637924

Gnomad4 AFR exome AF: 0.198

Gnomad4 AMR exome AF: 0.410

Gnomad4 ASJ exome AF: 0.383

Gnomad4 EAS exome AF: 0.369

Gnomad4 SAS exome AF: 0.335

Gnomad4 FIN exome AF: 0.298

Gnomad4 NFE exome AF: 0.403

Gnomad4 OTH exome AF: 0.390

GnomAD4 genome AF: 0.343 AC: 52181 AN: 152096 Hom.: 9547 Cov.: 33 AF XY: 0.342 AC XY: 25407 AN XY: 74364

Gnomad4 AFR AF: 0.211

Gnomad4 AMR AF: 0.428

Gnomad4 ASJ AF: 0.394

Gnomad4 EAS AF: 0.390

Gnomad4 SAS AF: 0.347

Gnomad4 FIN AF: 0.286

Gnomad4 NFE AF: 0.404

Gnomad4 OTH AF: 0.383

Alfa AF: 0.245 Hom.: 631

Bravo AF: 0.351

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	16
DANN	Benign	0.82
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs2292555; hg19: chr2-219146882;