chr4-182766636-T-C

Variant names:

• chr4-182766636-T-C
• rs10017238
• NM_001080477.4:c.4893-6836T>C

Variant summary

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

The NM_001080477.4(TENM3):​c.4893-6836T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 152,064 control chromosomes in the GnomAD database, including 2,642 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 0.17 (2642 hom., cov: 32)
• Consequence: TENM3 NM_001080477.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0170
• Publications: 3 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

LOC105377571 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080477.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TENM3	NM_001080477.4	MANE Select	c.4893-6836T>C		intron	N/A	NP_001073946.1
	TENM3	NM_001415969.1		c.4914-6836T>C		intron	N/A	NP_001402898.1
	TENM3	NM_001415970.1		c.4914-6836T>C		intron	N/A	NP_001402899.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TENM3	ENST00000511685.6	TSL:5 MANE Select	c.4893-6836T>C		intron	N/A	ENSP00000424226.1
	TENM3	ENST00000851056.1		c.4962-6836T>C		intron	N/A	ENSP00000521125.1
	TENM3	ENST00000851057.1		c.4959-6836T>C		intron	N/A	ENSP00000521126.1

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25899 AN: 151946 Hom.: 2630 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.0989

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.319

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.171 AC: 25940 AN: 152064 Hom.: 2642 Cov.: 32 AF XY: 0.180 AC XY: 13351 AN XY: 74310

African (AFR) AF: 0.137 AC: 5680 AN: 41488

American (AMR) AF: 0.255 AC: 3895 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 432 AN: 3470

East Asian (EAS) AF: 0.319 AC: 1643 AN: 5150

South Asian (SAS) AF: 0.191 AC: 919 AN: 4822

European-Finnish (FIN) AF: 0.291 AC: 3068 AN: 10560

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.145 AC: 9856 AN: 67982

Other (OTH) AF: 0.160 AC: 337 AN: 2112

Alfa AF: 0.153 Hom.: 4326

Bravo AF: 0.168

Asia WGS AF: 0.233 AC: 808 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	9.6
DANN	Benign	0.89
PhyloP100		0.017
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: rs10017238; hg19: chr4-183687789;