4-182058201-A-G

Variant names:

• chr4-182058201-A-G
• rs335077
• ENST00000507869.7:n.521+23555T>C

Variant summary

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

The ENST00000507869.7(TENM3-AS1):​n.521+23555T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 148,614 control chromosomes in the GnomAD database, including 16,549 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 0.42 (16549 hom., cov: 28)
• Consequence: TENM3-AS1 ENST00000507869.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36
• Publications: 1 publications found

Genes affected

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

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM3	XM_017008385.2	c.-76+16458A>G		intron_variant	Intron 4 of 32		XP_016863874.1
TENM3	XM_047415933.1	c.-76+16458A>G		intron_variant	Intron 4 of 32		XP_047271889.1
TENM3	XM_017008389.2	c.-76+16458A>G		intron_variant	Intron 4 of 32		XP_016863878.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TENM3-AS1	ENST00000507869.7	n.521+23555T>C		intron_variant	Intron 3 of 5	2
TENM3-AS1	ENST00000509012.5	n.220+23555T>C		intron_variant	Intron 2 of 4	4
TENM3-AS1	ENST00000669431.2	n.666+23555T>C		intron_variant	Intron 4 of 5

Frequencies

GnomAD3 genomes AF: 0.423 AC: 62767 AN: 148492 Hom.: 16505 Cov.: 28

Gnomad AFR AF: 0.745

Gnomad AMI AF: 0.361

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.413

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.395

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

GnomAD4 genome AF: 0.423 AC: 62865 AN: 148614 Hom.: 16549 Cov.: 28 AF XY: 0.415 AC XY: 29896 AN XY: 72020

African (AFR) AF: 0.746 AC: 30292 AN: 40628

American (AMR) AF: 0.291 AC: 4307 AN: 14786

Ashkenazi Jewish (ASJ) AF: 0.415 AC: 1429 AN: 3444

East Asian (EAS) AF: 0.257 AC: 1257 AN: 4900

South Asian (SAS) AF: 0.305 AC: 1428 AN: 4676

European-Finnish (FIN) AF: 0.268 AC: 2501 AN: 9324

Middle Eastern (MID) AF: 0.422 AC: 119 AN: 282

European-Non Finnish (NFE) AF: 0.301 AC: 20377 AN: 67588

Other (OTH) AF: 0.398 AC: 832 AN: 2092

Alfa AF: 0.384 Hom.: 4848

Bravo AF: 0.440

Asia WGS AF: 0.321 AC: 1115 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.043
DANN	Benign	0.39
PhyloP100		-1.4

Splicing

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

Other links and lift over

dbSNP: rs335077; hg19: chr4-182979354;