rs10520514

Variant names:

• chr4-181861392-T-A
• rs10520514
• ENST00000715797.1:n.187+13043A>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000715797.1(TENM3-AS1):​n.187+13043A>T variant causes a intron change. The variant allele was found at a frequency of 0.309 in 152,020 control chromosomes in the GnomAD database, including 8,100 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 0.31 (8100 hom., cov: 32)
• Consequence: TENM3-AS1 ENST00000715797.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.26
• Publications: 6 publications found

Genes affected

TENM3-AS1 (HGNC:28076): (TENM3 antisense RNA 1)

ENSG00000299420 (HGNC:):

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM3	XM_017008385.2	c.-236-6360T>A		intron_variant	Intron 2 of 32		XP_016863874.1
TENM3	XM_047415933.1	c.-236-6360T>A		intron_variant	Intron 2 of 32		XP_047271889.1
TENM3	XM_017008389.2	c.-236-6360T>A		intron_variant	Intron 2 of 32		XP_016863878.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TENM3-AS1	ENST00000715797.1	n.187+13043A>T		intron_variant	Intron 2 of 5
ENSG00000299420	ENST00000763321.1	n.568-6360T>A		intron_variant	Intron 5 of 6
ENSG00000299420	ENST00000763322.1	n.165-6360T>A		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46945 AN: 151902 Hom.: 8097 Cov.: 32

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.301

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.318

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

GnomAD4 genome AF: 0.309 AC: 46963 AN: 152020 Hom.: 8100 Cov.: 32 AF XY: 0.308 AC XY: 22851 AN XY: 74312

African (AFR) AF: 0.162 AC: 6713 AN: 41490

American (AMR) AF: 0.337 AC: 5144 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 1336 AN: 3468

East Asian (EAS) AF: 0.161 AC: 833 AN: 5160

South Asian (SAS) AF: 0.387 AC: 1865 AN: 4824

European-Finnish (FIN) AF: 0.372 AC: 3932 AN: 10572

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.384 AC: 26110 AN: 67920

Other (OTH) AF: 0.317 AC: 671 AN: 2116

Alfa AF: 0.353 Hom.: 1216

Bravo AF: 0.301

Asia WGS AF: 0.272 AC: 944 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	17
DANN	Benign	0.67
PhyloP100		5.3

Splicing

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

Other links and lift over

dbSNP: rs10520514; hg19: chr4-182782545;