chr4-36282026-A-C

Variant names:

• chr4-36282026-A-C
• NM_001170700.3:c.268A>C

Variant summary

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

The NM_001170700.3(DTHD1):​c.268A>C​(p.Lys90Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DTHD1 NM_001170700.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.02
• Publications: 0 publications found

Genes affected

DTHD1 (HGNC:37261): (death domain containing 1) This gene encodes a protein which contains a death domain. Death domain-containing proteins function in signaling pathways and formation of signaling complexes, as well as the apoptosis pathway. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2012]

DTHD1 Gene-Disease associations (from GenCC):

• LCAT deficiency

  Inheritance: AR Classification: LIMITED Submitted by: Franklin by Genoox

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=0.1298384).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001170700.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DTHD1	NM_001170700.3	MANE Select	c.268A>C	p.Lys90Gln	missense	Exon 1 of 10	NP_001164171.2	A0A1W2PR94
	DTHD1	NM_001136536.5		c.14A>C	p.Lys5Thr	missense	Exon 1 of 9	NP_001130008.2	Q6ZMT9-2
	DTHD1	NM_001378435.1		c.14A>C	p.Lys5Thr	missense	Exon 1 of 8	NP_001365364.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DTHD1	ENST00000639862.2	TSL:5 MANE Select	c.268A>C	p.Lys90Gln	missense	Exon 1 of 10	ENSP00000492542.1	A0A1W2PR94
	DTHD1	ENST00000903021.1		c.268A>C	p.Lys90Gln	missense	Exon 1 of 11	ENSP00000573080.1
	DTHD1	ENST00000903020.1		c.268A>C	p.Lys90Gln	missense	Exon 1 of 11	ENSP00000573079.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	13
DANN	Uncertain	0.98
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.13	T
PhyloP100		1.0
ClinPred		0.84	D
GERP RS		2.6
PromoterAI		-0.0061	Neutral
Mutation Taster		=93/7	polymorphism

Splicing

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

Other links and lift over

hg19: chr4-36283648;