ENST00000670601.1:n.124+4215C>G

Variant names:

• chr4-181695804-G-C
• rs7697691
• ENST00000670601.1:n.124+4215C>G

Variant summary

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

The ENST00000670601.1(ENSG00000287948):​n.124+4215C>G variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ENSG00000287948 ENST00000670601.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.796
• Publications: 4 publications found

Genes affected

ENSG00000287948 (HGNC:):

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: 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 (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM3	XM_017008385.2	c.-399-43683G>C		intron_variant	Intron 1 of 32		XP_016863874.1
TENM3	XM_047415933.1	c.-399-43683G>C		intron_variant	Intron 1 of 32		XP_047271889.1
TENM3	XM_017008389.2	c.-399-43683G>C		intron_variant	Intron 1 of 32		XP_016863878.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000287948	ENST00000670601.1	n.124+4215C>G		intron_variant	Intron 1 of 1
ENSG00000299420	ENST00000763321.1	n.247-43683G>C		intron_variant	Intron 3 of 6

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.070
DANN	Benign	0.33
PhyloP100		-0.80

Splicing

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

Other links and lift over

dbSNP: rs7697691; hg19: chr4-182616957;