rs908084

chr4-182622495-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
TENM3	NM_001080477.4	c.750-6156G>A		intron_variant		ENST00000511685.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TENM3	ENST00000511685.6	c.750-6156G>A		intron_variant		5	NM_001080477.4	P1
TENM3	ENST00000510504.1	c.324-6156G>A		intron_variant		3

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

Gnomad4 AFR AF: 0.0810

Gnomad4 AMR AF: 0.119

Gnomad4 ASJ AF: 0.120

Gnomad4 EAS AF: 0.228

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.0544

Gnomad4 OTH AF: 0.0870

Alfa AF: 0.0703 Hom.: 284

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs908084; hg19: chr4-183543648;