Variant 9-136717674-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_152421.4(DIPK1B):c.161C>T(p.Ser54Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000129 in 1,610,334 control chromosomes in the GnomAD database, including 1 homozygotes. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 1 hom. )

Consequence

DIPK1B
NM_152421.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.33

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DIPK1B	NM_152421.4 link	c.161C>T	p.Ser54Leu	missense_variant	2/5	ENST00000371692.9	NP_689634.2	Q5VUD6-1
LOC124900276	XM_047424334.1 link	c.*1666G>A		3_prime_UTR_variant	5/5		XP_047280290.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DIPK1B	ENST00000371692.9 link	c.161C>T	p.Ser54Leu	missense_variant	2/5	1	NM_152421.4	ENSP00000360757.4		Q5VUD6-1

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000604

AC:

AN:

248162

Hom.:

AF XY:

0.0000520

AC XY:

AN XY:

134668

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000514

Gnomad NFE exome

AF:

0.0000975

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000133

AC:

194

AN:

1458094

Hom.:

Cov.:

AF XY:

0.000123

AC XY:

AN XY:

725538

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000402

Gnomad4 NFE exome

AF:

0.000158

Gnomad4 OTH exome

AF:

0.000232

GnomAD4 genome

AF:

0.0000920

AC:

AN:

152240

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000119

Hom.:

Bravo

AF:

0.000102

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000577

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.00

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

Oct 26, 2022

The c.161C>T (p.S54L) alteration is located in exon 2 (coding exon 2) of the FAM69B gene. This alteration results from a C to T substitution at nucleotide position 161, causing the serine (S) at amino acid position 54 to be replaced by a leucine (L). 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

0.12

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

0.0077

Eigen_PC

Benign

-0.0038

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.084

MetaRNN

Uncertain

0.53

MetaSVM

Benign

-0.95

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.9

REVEL

Benign

0.14

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.022

Vest4

0.63

MVP

0.74

MPC

0.21

ClinPred

0.14

GERP RS

3.8

gMVP

0.67

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