rs1371217

Positions:

• chr4-181594506-T-A
• chr4-181594506-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_017008385.2(TENM3):​c.-399-144981T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 151,868 control chromosomes in the GnomAD database, including 18,195 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 0.49 (18195 hom., cov: 31)
• Consequence: TENM3 XM_017008385.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.482

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TENM3	XM_017008385.2	c.-399-144981T>A		intron_variant			XP_016863874.1
TENM3	XM_017008389.2	c.-399-144981T>A		intron_variant			XP_016863878.1
TENM3	XM_017008390.2	c.-399-144981T>A		intron_variant			XP_016863879.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.487 AC: 73868 AN: 151750 Hom.: 18188 Cov.: 31

Gnomad AFR AF: 0.456

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.494

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.395

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.462

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

GnomAD4 genome AF: 0.487 AC: 73890 AN: 151868 Hom.: 18195 Cov.: 31 AF XY: 0.484 AC XY: 35944 AN XY: 74192

Gnomad4 AFR AF: 0.456

Gnomad4 AMR AF: 0.494

Gnomad4 ASJ AF: 0.494

Gnomad4 EAS AF: 0.473

Gnomad4 SAS AF: 0.413

Gnomad4 FIN AF: 0.470

Gnomad4 NFE AF: 0.513

Gnomad4 OTH AF: 0.456

Alfa AF: 0.344 Hom.: 886

Bravo AF: 0.487

Asia WGS AF: 0.457 AC: 1589 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.1
DANN	Benign	0.53

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1371217; hg19: chr4-182515659;