chr4-182651237-C-T

Variant names:

• chr4-182651237-C-T
• rs6850978
• NM_001080477.4:c.989-2534C>T

Variant summary

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

The NM_001415969.1(TENM3):​c.989-2534C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 151,970 control chromosomes in the GnomAD database, including 14,671 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 0.43 (14671 hom., cov: 32)
• Consequence: TENM3 NM_001415969.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.576
• Publications: 4 publications found

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]

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.833 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001415969.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TENM3	NM_001080477.4	MANE Select	c.989-2534C>T		intron	N/A	NP_001073946.1
	TENM3	NM_001415969.1		c.989-2534C>T		intron	N/A	NP_001402898.1
	TENM3	NM_001415970.1		c.989-2534C>T		intron	N/A	NP_001402899.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TENM3	ENST00000511685.6	TSL:5 MANE Select	c.989-2534C>T		intron	N/A	ENSP00000424226.1
	TENM3	ENST00000851056.1		c.989-2534C>T		intron	N/A	ENSP00000521125.1
	TENM3	ENST00000851057.1		c.989-2534C>T		intron	N/A	ENSP00000521126.1

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64540 AN: 151852 Hom.: 14648 Cov.: 32

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.461

Gnomad AMR AF: 0.587

Gnomad ASJ AF: 0.434

Gnomad EAS AF: 0.854

Gnomad SAS AF: 0.525

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.440

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

GnomAD4 genome AF: 0.425 AC: 64602 AN: 151970 Hom.: 14671 Cov.: 32 AF XY: 0.429 AC XY: 31877 AN XY: 74276

African (AFR) AF: 0.395 AC: 16372 AN: 41442

American (AMR) AF: 0.588 AC: 8982 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.434 AC: 1506 AN: 3468

East Asian (EAS) AF: 0.854 AC: 4410 AN: 5162

South Asian (SAS) AF: 0.524 AC: 2530 AN: 4826

European-Finnish (FIN) AF: 0.340 AC: 3586 AN: 10540

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.379 AC: 25745 AN: 67948

Other (OTH) AF: 0.440 AC: 927 AN: 2108

Alfa AF: 0.406 Hom.: 22183

Bravo AF: 0.445

Asia WGS AF: 0.655 AC: 2274 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	13
DANN	Benign	0.65
PhyloP100		0.58
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs6850978; hg19: chr4-183572390;