dbSNP rs1200523384: DIPK1B:p.Gln21Pro (chr9-136712727-A-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_152421.4(DIPK1B):c.62A>C(p.Gln21Pro) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000148 in 1,349,522 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 8.3e-7 ( 0 hom. )

Consequence

DIPK1B
NM_152421.4 missense, splice_region

Scores

Splicing: ADA: 0.2696

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.47

Publications

0 publications found

Variant links:

Genes affected

DIPK1B (HGNC:28290): (divergent protein kinase domain 1B) This gene encodes a member of the FAM69 family of cysteine-rich type II transmembrane proteins. These proteins localize to the endoplasmic reticulum but their specific functions are unknown. [provided by RefSeq, Nov 2011]

DIPK1B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152421.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIPK1B	NM_152421.4	MANE Select	c.62A>C	p.Gln21Pro	missense splice_region	Exon 1 of 5	NP_689634.2	Q5VUD6-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DIPK1B	ENST00000371692.9	TSL:1 MANE Select	c.62A>C	p.Gln21Pro	missense splice_region	Exon 1 of 5	ENSP00000360757.4	Q5VUD6-1
DIPK1B	ENST00000931511.1		c.62A>C	p.Gln21Pro	missense splice_region	Exon 1 of 5	ENSP00000601570.1
DIPK1B	ENST00000931512.1		c.62A>C	p.Gln21Pro	missense splice_region	Exon 1 of 5	ENSP00000601571.1

Frequencies

GnomAD3 genomes

AF:

0.00000660

AC:

AN:

151450

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

26788

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

8.35e-7

AC:

AN:

1198072

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

586680

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23812

American (AMR)

AF:

0.00

AC:

AN:

12542

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18118

East Asian (EAS)

AF:

0.00

AC:

AN:

27282

South Asian (SAS)

AF:

0.00

AC:

AN:

50800

European-Finnish (FIN)

AF:

0.00

AC:

AN:

27544

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3312

European-Non Finnish (NFE)

AF:

0.00000101

AC:

AN:

986304

Other (OTH)

AF:

0.00

AC:

AN:

48358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.00000660

AC:

AN:

151450

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73984

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41266

American (AMR)

AF:

0.0000656

AC:

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5062

South Asian (SAS)

AF:

0.00

AC:

AN:

4806

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10514

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67794

Other (OTH)

AF:

0.00

AC:

AN:

2076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Uncertain

0.024

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

(source)

DANN

Uncertain

0.98

Eigen

Benign

-0.069

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.71

M_CAP

Uncertain

0.23

MetaRNN

Uncertain

0.44

MetaSVM

Benign

-0.94

PhyloP100

1.5

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-1.9

REVEL

Benign

0.24

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.014

Vest4

0.44

MutPred

0.44

Gain of loop (P = 0.0045)

MVP

0.66

MPC

0.41

ClinPred

0.86

GERP RS

2.1

PromoterAI

0.070

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.76

Mutation Taster

=62/38

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.27

dbscSNV1_RF

Benign

0.58

SpliceAI score (max)

0.10

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over