4-182174165-C-T

Variant names:

• chr4-182174165-C-T
• rs6815990
• ENST00000513201.1:n.175+30004C>T

Variant summary

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

The NM_001415969.1(TENM3):​c.-76+30004C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 151,720 control chromosomes in the GnomAD database, including 27,847 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 0.60 (27847 hom., cov: 31)
• Consequence: TENM3 NM_001415969.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.380
• 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

ENSG00000248266 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001415969.1. 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_001415969.1		c.-76+30004C>T		intron	N/A	NP_001402898.1
	TENM3	NM_001415970.1		c.-76+29411C>T		intron	N/A	NP_001402899.1
	TENM3	NM_001415968.1		c.-76+29411C>T		intron	N/A	NP_001402897.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TENM3	ENST00000513201.1	TSL:1	n.175+30004C>T		intron	N/A
	TENM3	ENST00000851042.1		c.-76+30004C>T		intron	N/A	ENSP00000521111.1
	TENM3	ENST00000851043.1		c.-76+29411C>T		intron	N/A	ENSP00000521112.1

Frequencies

GnomAD3 genomes AF: 0.601 AC: 91047 AN: 151602 Hom.: 27829 Cov.: 31

Gnomad AFR AF: 0.549

Gnomad AMI AF: 0.595

Gnomad AMR AF: 0.488

Gnomad ASJ AF: 0.615

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.572

Gnomad FIN AF: 0.664

Gnomad MID AF: 0.552

Gnomad NFE AF: 0.666

Gnomad OTH AF: 0.573

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

GnomAD4 genome AF: 0.600 AC: 91096 AN: 151720 Hom.: 27847 Cov.: 31 AF XY: 0.597 AC XY: 44225 AN XY: 74134

African (AFR) AF: 0.549 AC: 22702 AN: 41356

American (AMR) AF: 0.487 AC: 7415 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.615 AC: 2133 AN: 3470

East Asian (EAS) AF: 0.383 AC: 1972 AN: 5150

South Asian (SAS) AF: 0.573 AC: 2761 AN: 4818

European-Finnish (FIN) AF: 0.664 AC: 6969 AN: 10494

Middle Eastern (MID) AF: 0.549 AC: 158 AN: 288

European-Non Finnish (NFE) AF: 0.666 AC: 45240 AN: 67900

Other (OTH) AF: 0.572 AC: 1205 AN: 2108

Alfa AF: 0.646 Hom.: 3948

Bravo AF: 0.579

Asia WGS AF: 0.492 AC: 1701 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.2
DANN	Benign	0.56
PhyloP100		0.38

Splicing

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

Other links and lift over

dbSNP: rs6815990; hg19: chr4-183095318;