NM_001170700.3:c.392C>T

Variant names:

• chr4-36284096-C-T
• rs931094405
• NM_001170700.3:c.392C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001170700.3(DTHD1):​c.392C>T​(p.Thr131Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000361 in 1,384,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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)
  • Exomes 𝑓: 0.0000036 (0 hom.)
• Consequence: DTHD1 NM_001170700.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.247
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06068006).

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.392C>T	p.Thr131Ile	missense	Exon 2 of 10	NP_001164171.2	A0A1W2PR94
	DTHD1	NM_001136536.5		c.17+2067C>T		intron	N/A	NP_001130008.2	Q6ZMT9-2
	DTHD1	NM_001378435.1		c.17+2067C>T		intron	N/A	NP_001365364.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DTHD1	ENST00000639862.2	TSL:5 MANE Select	c.392C>T	p.Thr131Ile	missense	Exon 2 of 10	ENSP00000492542.1	A0A1W2PR94
	DTHD1	ENST00000507598.5	TSL:1	c.137C>T	p.Thr46Ile	missense	Exon 1 of 9	ENSP00000424426.1	D6RB49
	DTHD1	ENST00000456874.3	TSL:1	c.17C>T	p.Thr6Ile	missense	Exon 1 of 9	ENSP00000401597.2	Q6ZMT9-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000144 AC: 2 AN: 138944 AF XY: 0.0000134

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000180

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000361 AC: 5 AN: 1384890 Hom.: 0 Cov.: 30 AF XY: 0.00000439 AC XY: 3 AN XY: 683360

African (AFR) AF: 0.00 AC: 0 AN: 31594

American (AMR) AF: 0.00 AC: 0 AN: 35700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25178

East Asian (EAS) AF: 0.00 AC: 0 AN: 35722

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35000

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.00000278 AC: 3 AN: 1078856

Other (OTH) AF: 0.0000173 AC: 1 AN: 57912

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	4.7
DANN	Benign	0.87
DEOGEN2	Benign	0.0042	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.041	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.25
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.91	N
REVEL	Benign	0.013
Sift	Benign	0.12	T
Sift4G	Uncertain	0.020	D
Vest4		0.067
MutPred		0.19		Gain of glycosylation at T6 (P = 0.0148)
MVP		0.014
ClinPred		0.029	T
GERP RS		-0.46
PromoterAI		0.0014	Neutral
Varity_R		0.042
gMVP		0.69
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs931094405; hg19: chr4-36285718;