Variant chr13-42155370-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2

The NM_001297429.2(DGKH):c.-39C>A variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.0000048 in 1,459,356 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: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

DGKH
NM_001297429.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.09

Variant links:

Genes affected

DGKH (HGNC:2854): (diacylglycerol kinase eta) This gene encodes a member of the diacylglycerol kinase (DGK) enzyme family. Members of this family are involved in regulating intracellular concentrations of diacylglycerol and phosphatidic acid. Variation in this gene has been associated with bipolar disorder. Alternatively spliced transcript variants have been identified. [provided by RefSeq, Jul 2014]

DGKH links:

DGKH (HGNC:):

DGKH links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.837

BS2

High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DGKH	NM_178009.5 linkuse as main transcript	c.464C>A	p.Ser155Tyr	missense_variant	4/30	ENST00000337343.9	NP_821077.1	Q86XP1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DGKH	ENST00000337343.9 linkuse as main transcript	c.464C>A	p.Ser155Tyr	missense_variant	4/30	1	NM_178009.5	ENSP00000337572.4		Q86XP1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000480

AC:

AN:

1459356

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

725854

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:

0.00000630

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000756

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 21, 2023

The c.464C>A (p.S155Y) alteration is located in exon 4 (coding exon 4) of the DGKH gene. This alteration results from a C to A substitution at nucleotide position 464, causing the serine (S) at amino acid position 155 to be replaced by a tyrosine (Y). 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

0.24

BayesDel_addAF

Pathogenic

0.36

BayesDel_noAF

Pathogenic

0.27

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.63

.;D;.;.;.

Eigen

Pathogenic

0.71

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

D;D;.;D;D

M_CAP

Uncertain

0.14

MetaRNN

Pathogenic

0.84

D;D;D;D;D

MetaSVM

Uncertain

0.34

MutationAssessor

Uncertain

2.5

M;M;M;.;.

PrimateAI

Uncertain

0.78

PROVEAN

Uncertain

-3.7

.;D;D;.;D

REVEL

Uncertain

0.44

Sift

Uncertain

0.0010

.;D;D;.;D

Sift4G

Uncertain

0.0050

D;D;D;D;D

Polyphen

0.89

P;P;P;.;D

Vest4

0.90

MutPred

0.60

Loss of disorder (P = 0.0182);Loss of disorder (P = 0.0182);Loss of disorder (P = 0.0182);.;.;

MVP

0.89

MPC

0.64

ClinPred

0.98

GERP RS

6.0

Varity_R

0.55

gMVP

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.28

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.28

Position offset: -3

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