Variant chr18-74436542-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001044369.3(DIPK1C):c.1219C>A(p.Leu407Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,452,940 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

DIPK1C
NM_001044369.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.11

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.41615516).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DIPK1C	NM_001044369.3 linkuse as main transcript	c.1219C>A	p.Leu407Ile	missense_variant	4/4	ENST00000343998.8	NP_001037834.2	Q0P6D2-1
DIPK1C	XM_017025551.3 linkuse as main transcript	c.796C>A	p.Leu266Ile	missense_variant	4/4		XP_016881040.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DIPK1C	ENST00000343998.8 linkuse as main transcript	c.1219C>A	p.Leu407Ile	missense_variant	4/4	5	NM_001044369.3	ENSP00000344331.6		Q0P6D2-1
DIPK1C	ENST00000400291.2 linkuse as main transcript	c.322C>A	p.Leu108Ile	missense_variant	3/3	1		ENSP00000383148.2		Q0P6D2-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000427

AC:

AN:

234440

Hom.:

AF XY:

0.00000785

AC XY:

AN XY:

127344

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000945

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1452940

Hom.:

Cov.:

AF XY:

0.00000415

AC XY:

AN XY:

722078

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000828

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Jul 19, 2023

The c.1219C>A (p.L407I) alteration is located in exon 4 (coding exon 4) of the FAM69C gene. This alteration results from a C to A substitution at nucleotide position 1219, causing the leucine (L) at amino acid position 407 to be replaced by an isoleucine (I). 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

0.26

BayesDel_addAF

Benign

-0.051

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

0.17

Eigen_PC

Benign

0.012

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.68

T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.42

T;T

MetaSVM

Benign

-0.53

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.3

N;N

REVEL

Uncertain

0.33

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Vest4

0.51

MutPred

0.63

Loss of disorder (P = 0.0497);.;

MVP

0.39

MPC

0.48

ClinPred

0.91

GERP RS

3.1

gMVP

0.30

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