Variant chr9-136723031-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152421.4(DIPK1B):c.553A>G(p.Lys185Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000942 in 1,613,322 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000090 ( 0 hom. )

Consequence

DIPK1B
NM_152421.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.465

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:

LOC124900276 (HGNC:):

LOC124900276 links:

SNHG7 (HGNC:28254): (small nucleolar RNA host gene 7)

SNHG7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09766775).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DIPK1B	NM_152421.4 link	c.553A>G	p.Lys185Glu	missense_variant	5/5	ENST00000371692.9	NP_689634.2	Q5VUD6-1
LOC124900276	XM_047424334.1 link	c.-2756T>C		5_prime_UTR_variant	5/5		XP_047280290.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DIPK1B	ENST00000371692.9 link	c.553A>G	p.Lys185Glu	missense_variant	5/5	1	NM_152421.4	ENSP00000360757.4	Q5VUD6-1
DIPK1B	ENST00000371691.5 link	c.292A>G	p.Lys98Glu	missense_variant	3/3	1		ENSP00000360756.1	Q5VUD6-2
SNHG7	ENST00000414282.5 link	n.692T>C		non_coding_transcript_exon_variant	6/6	2

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000140

AC:

AN:

250324

Hom.:

AF XY:

0.000155

AC XY:

AN XY:

135608

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000926

Gnomad NFE exome

AF:

0.000159

Gnomad OTH exome

AF:

0.000818

GnomAD4 exome

AF:

0.0000897

AC:

131

AN:

1461112

Hom.:

Cov.:

AF XY:

0.000105

AC XY:

AN XY:

726870

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000380

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000380

Gnomad4 NFE exome

AF:

0.0000989

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.000138

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000121

Hom.:

Bravo

AF:

0.0000869

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.000124

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000296

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 09, 2023

The c.553A>G (p.K185E) alteration is located in exon 5 (coding exon 5) of the FAM69B gene. This alteration results from a A to G substitution at nucleotide position 553, causing the lysine (K) at amino acid position 185 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.42

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.90

D;D

M_CAP

Benign

0.037

MetaRNN

Benign

0.098

T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.13

Sift

Uncertain

0.019

D;D

Sift4G

Uncertain

0.044

D;D

Vest4

0.065

MVP

0.47

MPC

0.19

ClinPred

0.048

GERP RS

-2.6

gMVP

0.59

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over