Variant 18-74442092-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001044369.3(DIPK1C):c.901G>A(p.Ala301Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,158 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Consequence

DIPK1C
NM_001044369.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.50

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.792

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DIPK1C	NM_001044369.3 linkuse as main transcript	c.901G>A	p.Ala301Thr	missense_variant	3/4	ENST00000343998.8	NP_001037834.2	Q0P6D2-1
DIPK1C	XM_017025551.3 linkuse as main transcript	c.478G>A	p.Ala160Thr	missense_variant	3/4		XP_016881040.1
DIPK1C	XM_047437299.1 linkuse as main transcript	c.*11G>A		3_prime_UTR_variant	3/3		XP_047293255.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DIPK1C	ENST00000343998.8 linkuse as main transcript	c.901G>A	p.Ala301Thr	missense_variant	3/4	5	NM_001044369.3	ENSP00000344331.6		Q0P6D2-1
DIPK1C	ENST00000400291.2 linkuse as main transcript	c.4G>A	p.Ala2Thr	missense_variant	2/3	1		ENSP00000383148.2		Q0P6D2-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152158

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:

0.000193

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

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152158

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

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

Mar 03, 2023

The c.901G>A (p.A301T) alteration is located in exon 3 (coding exon 3) of the FAM69C gene. This alteration results from a G to A substitution at nucleotide position 901, causing the alanine (A) at amino acid position 301 to be replaced by a threonine (T). 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

Uncertain

0.37

BayesDel_addAF

Uncertain

0.094

BayesDel_noAF

Benign

-0.10

CADD

Pathogenic

DANN

Pathogenic

1.0

Eigen

Pathogenic

0.77

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.87

D;D

M_CAP

Benign

0.020

MetaRNN

Pathogenic

0.79

D;D

MetaSVM

Benign

-1.1

PrimateAI

Uncertain

0.79

PROVEAN

Benign

-2.2

N;N

REVEL

Uncertain

0.30

Sift

Benign

0.13

T;T

Sift4G

Pathogenic

0.0

D;D

Vest4

0.90

MutPred

0.62

Loss of helix (P = 0.0558);.;

MVP

0.53

MPC

0.45

ClinPred

0.99

GERP RS

5.4

gMVP

0.68

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