rs10866256

Variant names:

• chr4-182731022-C-A
• rs10866256
• NM_001080477.4:c.2850C>A

Your query was ambiguous. Multiple possible variants found:

• chr4-182731022-C-A
• chr4-182731022-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000511685.6(TENM3):​c.2850C>A​(p.Asp950Glu) 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. 7/10 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D950N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: TENM3 ENST00000511685.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.66
• Publications: 14 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: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• microphthalmia, isolated, with coloboma

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.090435386).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000511685.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TENM3	NM_001080477.4	MANE Select	c.2850C>A	p.Asp950Glu	missense	Exon 16 of 28	NP_001073946.1
	TENM3	NM_001415969.1		c.2850C>A	p.Asp950Glu	missense	Exon 16 of 29	NP_001402898.1
	TENM3	NM_001415970.1		c.2850C>A	p.Asp950Glu	missense	Exon 16 of 29	NP_001402899.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TENM3	ENST00000511685.6	TSL:5 MANE Select	c.2850C>A	p.Asp950Glu	missense	Exon 16 of 28	ENSP00000424226.1
	TENM3	ENST00000502950.1	TSL:2	n.1237C>A		non_coding_transcript_exon	Exon 8 of 15

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_noAF	Pathogenic	0.18
CADD	Benign	17
DEOGEN2	Benign	0.064	T
LIST_S2	Benign	0.75	T
MetaRNN	Benign	0.090	T
PhyloP100		1.7
PROVEAN	Benign	-0.64	N
Sift	Benign	0.65	T
Sift4G	Benign	0.31	T
Vest4		0.14
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs10866256; hg19: chr4-183652175;