rs6815916

Variant names:

• chr4-181631890-A-G
• rs6815916
• ENST00000763321.1:n.126-2058A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000763321.1(ENSG00000299420):​n.126-2058A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0892 in 152,162 control chromosomes in the GnomAD database, including 641 homozygotes. 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: 𝑓 0.089 (641 hom., cov: 32)
• Consequence: ENSG00000299420 ENST00000763321.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51
• Publications: 8 publications found

Genes affected

ENSG00000299420 (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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM3	XM_017008385.2	c.-399-107597A>G		intron_variant	Intron 1 of 32		XP_016863874.1
TENM3	XM_017008389.2	c.-399-107597A>G		intron_variant	Intron 1 of 32		XP_016863878.1
TENM3	XM_017008390.2	c.-399-107597A>G		intron_variant	Intron 1 of 31		XP_016863879.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000299420	ENST00000763321.1	n.126-2058A>G		intron_variant	Intron 2 of 6

Frequencies

GnomAD3 genomes AF: 0.0892 AC: 13567 AN: 152044 Hom.: 640 Cov.: 32

Gnomad AFR AF: 0.0998

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.0531

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.0752

Gnomad MID AF: 0.0669

Gnomad NFE AF: 0.0858

Gnomad OTH AF: 0.0881

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

GnomAD4 genome AF: 0.0892 AC: 13579 AN: 152162 Hom.: 641 Cov.: 32 AF XY: 0.0900 AC XY: 6696 AN XY: 74382

African (AFR) AF: 0.0998 AC: 4144 AN: 41508

American (AMR) AF: 0.0530 AC: 811 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 355 AN: 3462

East Asian (EAS) AF: 0.145 AC: 749 AN: 5158

South Asian (SAS) AF: 0.124 AC: 600 AN: 4820

European-Finnish (FIN) AF: 0.0752 AC: 797 AN: 10598

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0858 AC: 5837 AN: 68006

Other (OTH) AF: 0.0872 AC: 184 AN: 2110

Alfa AF: 0.0887 Hom.: 1886

Bravo AF: 0.0873

Asia WGS AF: 0.136 AC: 473 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.24
DANN	Benign	0.50
PhyloP100		-1.5

Splicing

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

Other links and lift over

dbSNP: rs6815916; hg19: chr4-182553043;