dbSNP rs992157: PNKD:c.236+18509G>A (chr2-218290058-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015488.5(PNKD):c.236+18509G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 151,978 control chromosomes in the GnomAD database, including 18,603 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 0.47 ( 18601 hom., cov: 31)

Exomes 𝑓: 0.46 ( 2 hom. )

Consequence

PNKD
NM_015488.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.500

Publications

48 publications found

Variant links:

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]

PNKD links:

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]

TMBIM1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PNKD	NM_015488.5 link	c.236+18509G>A		intron_variant	Intron 2 of 9	ENST00000273077.9	NP_056303.3
TMBIM1	NM_022152.6 link	c.-41+2408C>T		intron_variant	Intron 1 of 11	ENST00000258412.8	NP_071435.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PNKD	ENST00000273077.9 link	c.236+18509G>A		intron_variant	Intron 2 of 9	1	NM_015488.5	ENSP00000273077.4
TMBIM1	ENST00000258412.8 link	c.-41+2408C>T		intron_variant	Intron 1 of 11	1	NM_022152.6	ENSP00000258412.3

Frequencies

GnomAD3 genomes

AF:

0.469

AC:

71153

AN:

151836

Hom.:

18580

Cov.:

show subpopulations

Gnomad AFR

AF:

0.221

Gnomad AMI

AF:

0.533

Gnomad AMR

AF:

0.483

Gnomad ASJ

AF:

0.514

Gnomad EAS

AF:

0.602

Gnomad SAS

AF:

0.633

Gnomad FIN

AF:

0.687

Gnomad MID

AF:

0.377

Gnomad NFE

AF:

0.558

Gnomad OTH

AF:

0.454

GnomAD4 exome

AF:

0.458

AC:

AN:

Hom.:

Cov.:

AF XY:

0.417

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.438

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.469

AC:

71196

AN:

151954

Hom.:

18601

Cov.:

AF XY:

0.475

AC XY:

35249

AN XY:

74254

show subpopulations

African (AFR)

AF:

0.221

AC:

9172

AN:

41426

American (AMR)

AF:

0.484

AC:

7388

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.514

AC:

1784

AN:

3470

East Asian (EAS)

AF:

0.602

AC:

3104

AN:

5156

South Asian (SAS)

AF:

0.632

AC:

3049

AN:

4822

European-Finnish (FIN)

AF:

0.687

AC:

7259

AN:

10570

Middle Eastern (MID)

AF:

0.384

AC:

113

AN:

294

European-Non Finnish (NFE)

AF:

0.558

AC:

37878

AN:

67932

Other (OTH)

AF:

0.456

AC:

963

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1748

3496

5245

6993

8741

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

656

1312

1968

2624

3280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.524

Hom.:

69112

Bravo

AF:

0.442

Asia WGS

AF:

0.623

AC:

2169

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.2

(source)

DANN

Benign

0.60

PhyloP100

0.50

PromoterAI

0.015

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over