rs10520540

chr4-182676681-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001080477.4(TENM3):c.1327-2985A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0186 in 152,328 control chromosomes in the GnomAD database, including 53 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 0.019 (53 hom., cov: 33)
• Consequence: TENM3 NM_001080477.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.135

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=-0.88).
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0186 (2838/152328) while in subpopulation EAS AF= 0.0526 (273/5188). AF 95% confidence interval is 0.0475. There are 53 homozygotes in gnomad4. There are 1588 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 53 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TENM3	NM_001080477.4	c.1327-2985A>G		intron_variant		ENST00000511685.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TENM3	ENST00000511685.6	c.1327-2985A>G		intron_variant		5	NM_001080477.4	P1

Frequencies

GnomAD3 genomes AF: 0.0187 AC: 2840 AN: 152210 Hom.: 53 Cov.: 33

Gnomad AFR AF: 0.00359

Gnomad AMI AF: 0.0352

Gnomad AMR AF: 0.0312

Gnomad ASJ AF: 0.0389

Gnomad EAS AF: 0.0527

Gnomad SAS AF: 0.0302

Gnomad FIN AF: 0.0557

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0142

Gnomad OTH AF: 0.0296

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

GnomAD4 genome AF: 0.0186 AC: 2838 AN: 152328 Hom.: 53 Cov.: 33 AF XY: 0.0213 AC XY: 1588 AN XY: 74482

Gnomad4 AFR AF: 0.00358

Gnomad4 AMR AF: 0.0310

Gnomad4 ASJ AF: 0.0389

Gnomad4 EAS AF: 0.0526

Gnomad4 SAS AF: 0.0303

Gnomad4 FIN AF: 0.0557

Gnomad4 NFE AF: 0.0142

Gnomad4 OTH AF: 0.0288

Alfa AF: 0.0156 Hom.: 9

Bravo AF: 0.0169

Asia WGS AF: 0.0400 AC: 141 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.60
Dann	Benign	0.74

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: rs10520540; hg19: chr4-183597834;