chr4-182622495-G-A

Variant names:

• chr4-182622495-G-A
• rs908084
• NM_001080477.4:c.750-6156G>A

Variant summary

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

The NM_001080477.4(TENM3):​c.750-6156G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0838 in 152,200 control chromosomes in the GnomAD database, including 675 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 0.084 (675 hom., cov: 31)
• Consequence: TENM3 NM_001080477.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.470
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM3	NM_001080477.4	c.750-6156G>A		intron_variant	Intron 4 of 27	ENST00000511685.6	NP_001073946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TENM3	ENST00000511685.6	c.750-6156G>A		intron_variant	Intron 4 of 27	5	NM_001080477.4	ENSP00000424226.1
TENM3	ENST00000510504.1	c.324-6156G>A		intron_variant	Intron 2 of 2	3		ENSP00000426914.1

Frequencies

GnomAD3 genomes AF: 0.0838 AC: 12745 AN: 152082 Hom.: 674 Cov.: 31

Gnomad AFR AF: 0.0811

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0544

Gnomad OTH AF: 0.0880

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

GnomAD4 genome AF: 0.0838 AC: 12751 AN: 152200 Hom.: 675 Cov.: 31 AF XY: 0.0882 AC XY: 6564 AN XY: 74404

African (AFR) AF: 0.0810 AC: 3365 AN: 41548

American (AMR) AF: 0.119 AC: 1825 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 415 AN: 3466

East Asian (EAS) AF: 0.228 AC: 1184 AN: 5182

South Asian (SAS) AF: 0.144 AC: 694 AN: 4816

European-Finnish (FIN) AF: 0.123 AC: 1297 AN: 10580

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0544 AC: 3697 AN: 68010

Other (OTH) AF: 0.0870 AC: 184 AN: 2114

Alfa AF: 0.0683 Hom.: 938

Bravo AF: 0.0871

Asia WGS AF: 0.204 AC: 710 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.20
DANN	Benign	0.53
PhyloP100		-0.47
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: rs908084; hg19: chr4-183543648;