rs1914369

Positions:

• chr4-181859415-G-A
• chr4-181859415-G-C
• chr4-181859415-G-T

Variant summary

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

The XM_017008385.2(TENM3):​c.-236-8337G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.778 in 151,948 control chromosomes in the GnomAD database, including 46,271 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 0.78 (46271 hom., cov: 30)
• Consequence: TENM3 XM_017008385.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.56

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=-0.67).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.927 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TENM3	XM_017008385.2	c.-236-8337G>A		intron_variant			XP_016863874.1
TENM3	XM_047415933.1	c.-236-8337G>A		intron_variant			XP_047271889.1
TENM3	XM_017008389.2	c.-236-8337G>A		intron_variant			XP_016863878.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.778 AC: 118080 AN: 151830 Hom.: 46229 Cov.: 30

Gnomad AFR AF: 0.826

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.795

Gnomad ASJ AF: 0.840

Gnomad EAS AF: 0.950

Gnomad SAS AF: 0.820

Gnomad FIN AF: 0.764

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.732

Gnomad OTH AF: 0.768

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

GnomAD4 genome AF: 0.778 AC: 118179 AN: 151948 Hom.: 46271 Cov.: 30 AF XY: 0.780 AC XY: 57892 AN XY: 74240

Gnomad4 AFR AF: 0.826

Gnomad4 AMR AF: 0.795

Gnomad4 ASJ AF: 0.840

Gnomad4 EAS AF: 0.950

Gnomad4 SAS AF: 0.820

Gnomad4 FIN AF: 0.764

Gnomad4 NFE AF: 0.731

Gnomad4 OTH AF: 0.772

Alfa AF: 0.746 Hom.: 71007

Bravo AF: 0.781

Asia WGS AF: 0.891 AC: 3100 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	11
DANN	Benign	0.46

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1914369; hg19: chr4-182780568;