4-182346812-ATG-GTT

Variant names:

• chr4-182346812-ATG-GTT
• NM_001080477.4:c.394_396delATGinsGTT
• TENM3 p.Met132Val

Variant summary

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

The NM_001080477.4(TENM3):​c.394_396delATGinsGTT​(p.Met132Val) variant causes a missense change. 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: 31)
• Consequence: TENM3 NM_001080477.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.27
• Publications: 0 publications found

Genes affected

TENM3 (HGNC:29944): (teneurin transmembrane protein 3) This gene encodes a member of the teneurin transmembrane protein family. The encoded protein may be involved in the regulation of neuronal development including development of the visual pathway. Mutations in this gene have been associated with microphthalmia and developmental dysplasia of the hip. [provided by RefSeq, Jan 2023]

TENM3 Gene-Disease associations (from GenCC):

• microphthalmia, isolated, with coloboma 9

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, PanelApp Australia
• microphthalmia, isolated, with coloboma

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080477.4. 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
	TENM3	NM_001080477.4	MANE Select	c.394_396delATGinsGTT	p.Met132Val	missense	N/A	NP_001073946.1	Q9P273
	TENM3	NM_001415969.1		c.394_396delATGinsGTT	p.Met132Val	missense	N/A	NP_001402898.1
	TENM3	NM_001415970.1		c.394_396delATGinsGTT	p.Met132Val	missense	N/A	NP_001402899.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TENM3	ENST00000511685.6	TSL:5 MANE Select	c.394_396delATGinsGTT	p.Met132Val	missense	N/A	ENSP00000424226.1	Q9P273
	TENM3	ENST00000513201.1	TSL:1	n.644_646delATGinsGTT		non_coding_transcript_exon	Exon 3 of 4
	TENM3	ENST00000851056.1		c.394_396delATGinsGTT	p.Met132Val	missense	N/A	ENSP00000521125.1

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.3

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: chr4-183267965;