rs10000076

Variant names:

• chr4-182367207-T-G
• rs10000076
• NM_001080477.4:c.511+20278T>G

Variant summary

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

The NM_001080477.4(TENM3):​c.511+20278T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.96 in 152,268 control chromosomes in the GnomAD database, including 70,221 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 0.96 (70221 hom., cov: 32)
• Consequence: TENM3 NM_001080477.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.39
• Publications: 1 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.981 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM3	NM_001080477.4	c.511+20278T>G		intron_variant	Intron 3 of 27	ENST00000511685.6	NP_001073946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TENM3	ENST00000511685.6	c.511+20278T>G		intron_variant	Intron 3 of 27	5	NM_001080477.4	ENSP00000424226.1

Frequencies

GnomAD3 genomes AF: 0.960 AC: 146014 AN: 152150 Hom.: 70169 Cov.: 32

Gnomad AFR AF: 0.909

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.973

Gnomad ASJ AF: 0.904

Gnomad EAS AF: 0.945

Gnomad SAS AF: 0.952

Gnomad FIN AF: 0.989

Gnomad MID AF: 0.968

Gnomad NFE AF: 0.987

Gnomad OTH AF: 0.960

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

GnomAD4 genome AF: 0.960 AC: 146124 AN: 152268 Hom.: 70221 Cov.: 32 AF XY: 0.959 AC XY: 71420 AN XY: 74454

African (AFR) AF: 0.909 AC: 37775 AN: 41540

American (AMR) AF: 0.973 AC: 14874 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.904 AC: 3139 AN: 3472

East Asian (EAS) AF: 0.945 AC: 4875 AN: 5160

South Asian (SAS) AF: 0.951 AC: 4589 AN: 4824

European-Finnish (FIN) AF: 0.989 AC: 10497 AN: 10612

Middle Eastern (MID) AF: 0.969 AC: 285 AN: 294

European-Non Finnish (NFE) AF: 0.987 AC: 67147 AN: 68046

Other (OTH) AF: 0.960 AC: 2031 AN: 2116

Alfa AF: 0.974 Hom.: 15016

Bravo AF: 0.956

Asia WGS AF: 0.959 AC: 3335 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.099
DANN	Benign	0.28
PhyloP100		-2.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs10000076; hg19: chr4-183288360;