rs2382818

chr2-218291184-A-T

Variant summary

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

The NM_015488.5(PNKD):c.236+19635A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 151,756 control chromosomes in the GnomAD database, including 10,248 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 0.36 (10248 hom., cov: 31)
• Consequence: PNKD NM_015488.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.824

Genes affected

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: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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PNKD	NM_015488.5	c.236+19635A>T		intron_variant		ENST00000273077.9
TMBIM1	NM_022152.6	c.-41+1282T>A		intron_variant		ENST00000258412.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMBIM1	ENST00000258412.8	c.-41+1282T>A		intron_variant		1	NM_022152.6	P1
PNKD	ENST00000273077.9	c.236+19635A>T		intron_variant		1	NM_015488.5

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54639 AN: 151638 Hom.: 10247 Cov.: 31

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.388

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.529

Gnomad NFE AF: 0.417

Gnomad OTH AF: 0.400

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.360 AC: 54647 AN: 151756 Hom.: 10248 Cov.: 31 AF XY: 0.357 AC XY: 26497 AN XY: 74160

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.437

Gnomad4 ASJ AF: 0.420

Gnomad4 EAS AF: 0.388

Gnomad4 SAS AF: 0.350

Gnomad4 FIN AF: 0.288

Gnomad4 NFE AF: 0.417

Gnomad4 OTH AF: 0.400

Alfa AF: 0.384 Hom.: 1443

Bravo AF: 0.368

Asia WGS AF: 0.316 AC: 1095 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	5.7
Dann	Benign	0.58

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: rs2382818; hg19: chr2-219155907;