4-36282039-CT-CTTT

Variant names:

• chr4-36282039-C-CTT
• rs372438791
• NM_001170700.3:c.271+17_271+18dupTT

Variant summary

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

The NM_001170700.3(DTHD1):​c.271+17_271+18dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000146 in 1,367,020 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: DTHD1 NM_001170700.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.226
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.271+17_271+18dupTT		intron	N/A	NP_001164171.2	A0A1W2PR94
	DTHD1	NM_001136536.5		c.17+17_17+18dupTT		intron	N/A	NP_001130008.2	Q6ZMT9-2
	DTHD1	NM_001378435.1		c.17+17_17+18dupTT		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.271+10_271+11insTT		intron	N/A	ENSP00000492542.1	A0A1W2PR94
	DTHD1	ENST00000903021.1		c.271+10_271+11insTT		intron	N/A	ENSP00000573080.1
	DTHD1	ENST00000903020.1		c.271+10_271+11insTT		intron	N/A	ENSP00000573079.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000146 AC: 2 AN: 1367020 Hom.: 0 Cov.: 29 AF XY: 0.00000148 AC XY: 1 AN XY: 674020

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30484

American (AMR) AF: 0.00 AC: 0 AN: 33026

Ashkenazi Jewish (ASJ) AF: 0.0000418 AC: 1 AN: 23900

East Asian (EAS) AF: 0.00 AC: 0 AN: 34778

South Asian (SAS) AF: 0.00 AC: 0 AN: 73838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5252

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1061726

Other (OTH) AF: 0.0000177 AC: 1 AN: 56390

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.23

Splicing

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

Other links and lift over

dbSNP: rs372438791; hg19: chr4-36283661;