Variant chr18-74446784-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001044369.3(DIPK1C):c.698G>A(p.Arg233Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00071 in 1,504,108 control chromosomes in the GnomAD database, including 1 homozygotes. 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 0.00037 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00075 ( 1 hom. )

Consequence

DIPK1C
NM_001044369.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.461

Variant links:

Genes affected

DIPK1C (HGNC:31729): (divergent protein kinase domain 1C) 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]

DIPK1C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.009761661).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DIPK1C	NM_001044369.3 linkuse as main transcript	c.698G>A	p.Arg233Lys	missense_variant	2/4	ENST00000343998.8	NP_001037834.2	Q0P6D2-1
DIPK1C	XM_047437299.1 linkuse as main transcript	c.698G>A	p.Arg233Lys	missense_variant	2/3		XP_047293255.1
DIPK1C	XM_017025551.3 linkuse as main transcript	c.275G>A	p.Arg92Lys	missense_variant	2/4		XP_016881040.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DIPK1C	ENST00000343998.8 linkuse as main transcript	c.698G>A	p.Arg233Lys	missense_variant	2/4	5	NM_001044369.3	ENSP00000344331.6		Q0P6D2-1
DIPK1C	ENST00000400291.2 linkuse as main transcript	c.-21-4668G>A		intron_variant		1		ENSP00000383148.2		Q0P6D2-2

Frequencies

GnomAD3 genomes

AF:

0.000368

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000764

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000269

AC:

AN:

115340

Hom.:

AF XY:

0.000366

AC XY:

AN XY:

60034

show subpopulations

Gnomad AFR exome

AF:

0.000135

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000143

Gnomad NFE exome

AF:

0.000618

Gnomad OTH exome

AF:

0.000312

GnomAD4 exome

AF:

0.000749

AC:

1012

AN:

1351914

Hom.:

Cov.:

AF XY:

0.000769

AC XY:

509

AN XY:

661826

show subpopulations

Gnomad4 AFR exome

AF:

0.0000666

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000632

Gnomad4 NFE exome

AF:

0.000930

Gnomad4 OTH exome

AF:

0.000467

GnomAD4 genome

AF:

0.000368

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.000256

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000764

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000456

Hom.:

Bravo

AF:

0.000329

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00104

AC:

ExAC

AF:

0.000246

AC:

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

Aug 08, 2023

The c.698G>A (p.R233K) alteration is located in exon 2 (coding exon 2) of the FAM69C gene. This alteration results from a G to A substitution at nucleotide position 698, causing the arginine (R) at amino acid position 233 to be replaced by a lysine (K). 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

0.084

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.81

CADD

Benign

3.6

DANN

Benign

0.70

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.066

LIST_S2

Benign

0.22

M_CAP

Benign

0.0046

MetaRNN

Benign

0.0098

MetaSVM

Benign

-0.93

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.16

REVEL

Benign

0.027

Sift

Benign

0.99

Sift4G

Benign

1.0

Vest4

0.025

MVP

0.085

MPC

0.085

ClinPred

0.0035

GERP RS

-1.8

gMVP

0.33

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