rs9993255

Variant names:

• chr4-181947687-G-A
• rs9993255
• ENST00000509012.5:n.378+64975C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000509012.5(TENM3-AS1):​n.378+64975C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 151,874 control chromosomes in the GnomAD database, including 7,278 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 0.29 (7278 hom., cov: 32)
• Consequence: TENM3-AS1 ENST00000509012.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.56
• Publications: 1 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM3	XM_017008385.2	c.-156+79855G>A		intron_variant	Intron 3 of 32		XP_016863874.1
TENM3	XM_047415933.1	c.-156+79855G>A		intron_variant	Intron 3 of 32		XP_047271889.1
TENM3	XM_017008389.2	c.-156+79855G>A		intron_variant	Intron 3 of 32		XP_016863878.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TENM3-AS1	ENST00000509012.5	n.378+64975C>T		intron_variant	Intron 3 of 4	4
ENSG00000299420	ENST00000763322.1	n.245+79855G>A		intron_variant	Intron 2 of 3
ENSG00000299420	ENST00000763323.1	n.245+79855G>A		intron_variant	Intron 2 of 3
ENSG00000299420	ENST00000763324.1	n.245+79855G>A		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44704 AN: 151756 Hom.: 7255 Cov.: 32

Gnomad AFR AF: 0.437

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.277

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

GnomAD4 genome AF: 0.295 AC: 44768 AN: 151874 Hom.: 7278 Cov.: 32 AF XY: 0.289 AC XY: 21463 AN XY: 74230

African (AFR) AF: 0.437 AC: 18102 AN: 41408

American (AMR) AF: 0.202 AC: 3081 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 810 AN: 3470

East Asian (EAS) AF: 0.176 AC: 911 AN: 5164

South Asian (SAS) AF: 0.234 AC: 1124 AN: 4812

European-Finnish (FIN) AF: 0.260 AC: 2735 AN: 10520

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.254 AC: 17227 AN: 67928

Other (OTH) AF: 0.283 AC: 597 AN: 2108

Alfa AF: 0.268 Hom.: 19399

Bravo AF: 0.297

Asia WGS AF: 0.267 AC: 929 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	6.2
DANN	Benign	0.46
PhyloP100		1.6

Splicing

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

Other links and lift over

dbSNP: rs9993255; hg19: chr4-182868840;