4-36284201-G-A

Position:

• chr4-36284201-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001170700.3(DTHD1):​c.497G>A​(p.Gly166Glu) 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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DTHD1 NM_001170700.3 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.155

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.057246685).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DTHD1	NM_001170700.3	c.497G>A	p.Gly166Glu	missense_variant	2/10	ENST00000639862.2	NP_001164171.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DTHD1	ENST00000639862.2	c.497G>A	p.Gly166Glu	missense_variant	2/10	5	NM_001170700.3	ENSP00000492542.1
DTHD1	ENST00000507598.5	c.242G>A	p.Gly81Glu	missense_variant	1/9	1		ENSP00000424426.1
DTHD1	ENST00000456874.3	c.122G>A	p.Gly41Glu	missense_variant	1/9	1		ENSP00000401597.2
DTHD1	ENST00000357504.7	c.17+2172G>A		intron_variant		2		ENSP00000350103.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Retinal dystrophy Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg

Jan 01, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	4.9
DANN	Benign	0.62
DEOGEN2	Benign	0.0010	.;.;T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.57	T;T;T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.057	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.71	.;.;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.28	.;N;N
REVEL	Benign	0.012
Sift	Benign	0.078	.;T;T
Sift4G	Benign	0.18	.;T;T
Vest4		0.097, 0.11
MutPred		0.24		.;.;Gain of glycosylation at Y46 (P = 0.0017);
MVP		0.061
ClinPred		0.043	T
GERP RS		0.093
Varity_R		0.055
gMVP		0.28

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-36285823;