1-95191650-ATG-GTA

Variant names:

• chr1-95191650-ATG-GTA
• NM_152487.3:c.574_576delATGinsGTA
• TLCD4 p.Met192Val

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_152487.3(TLCD4):​c.574_576delATGinsGTA​(p.Met192Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TLCD4 NM_152487.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.08
• Publications: 0 publications found

Genes affected

TLCD4 (HGNC:26477): (TLC domain containing 4) Predicted to be involved in lipid homeostasis. Predicted to be integral component of membrane. Predicted to be active in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

TLCD4-RWDD3 (HGNC:49388): (TLCD4-RWDD3 readthrough) This locus represents naturally occurring read-through transcription between the neighboring TMEM56 (transmembrane protein 56) and RWDD3 (RWD domain containing 3) genes on chromosome 1. The read-through transcript encodes a protein that shares sequence identity with the upstream gene product, but it contains a distinct C-terminus due to frameshifts versus the downstream gene coding sequence. [provided by RefSeq, Dec 2010]

RWDD3-DT (HGNC:55839): (RWDD3 divergent transcript)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152487.3. 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
	TLCD4	NM_152487.3	MANE Select	c.574_576delATGinsGTA	p.Met192Val	missense	N/A	NP_689700.1	Q96MV1
	TLCD4	NM_001199679.2		c.574_576delATGinsGTA	p.Met192Val	missense	N/A	NP_001186608.1	Q96MV1
	TLCD4-RWDD3	NM_001199691.1		c.473+17761_473+17763delATGinsGTA		intron	N/A	NP_001186620.1	S4R434

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLCD4	ENST00000370203.9	TSL:1 MANE Select	c.574_576delATGinsGTA	p.Met192Val	missense	N/A	ENSP00000359222.4	Q96MV1
	TLCD4-RWDD3	ENST00000604534.5	TSL:2	c.473+17761_473+17763delATGinsGTA		intron	N/A	ENSP00000475025.1	S4R434
	TLCD4	ENST00000882686.1		c.574_576delATGinsGTA	p.Met192Val	missense	N/A	ENSP00000552745.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.1

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-95657206;

Mutation Effect Viewer