rs1344286

Variant names:

• chr13-42127463-A-C
• rs1344286
• NM_178009.5:c.193A>C

Your query was ambiguous. Multiple possible variants found:

• chr13-42127463-A-C
• chr13-42127463-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_178009.5(DGKH):​c.193A>C​(p.Thr65Pro) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DGKH NM_178009.5 missense, splice_region
• Scores: Splicing: ADA: 0.3135
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.31
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22653326).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178009.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGKH	NM_178009.5	MANE Select	c.193A>C	p.Thr65Pro	missense splice_region	Exon 2 of 30	NP_821077.1
	DGKH	NM_001204504.3		c.193A>C	p.Thr65Pro	missense splice_region	Exon 3 of 30	NP_001191433.1
	DGKH	NM_152910.6		c.193A>C	p.Thr65Pro	missense splice_region	Exon 2 of 29	NP_690874.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGKH	ENST00000337343.9	TSL:1 MANE Select	c.193A>C	p.Thr65Pro	missense splice_region	Exon 2 of 30	ENSP00000337572.4
	DGKH	ENST00000261491.9	TSL:1	c.193A>C	p.Thr65Pro	missense splice_region	Exon 2 of 29	ENSP00000261491.4
	DGKH	ENST00000379274.6	TSL:2	c.193A>C	p.Thr65Pro	missense splice_region	Exon 3 of 30	ENSP00000368576.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Uncertain	0.084	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.040	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		7.3
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.18
Sift	Benign	0.082	T
Sift4G	Benign	0.24	T
Polyphen		1.0	D
Vest4		0.52
MutPred		0.27		Loss of phosphorylation at T65 (P = 0.0308)
MVP		0.49
MPC		1.3
ClinPred		0.97	D
GERP RS		5.5
Varity_R		0.42
gMVP		0.43
Mutation Taster		=37/63	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.31
dbscSNV1_RF	Benign	0.55
SpliceAI score (max)		0.14		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1344286; hg19: chr13-42701599;