4-182689758-A-C

Variant names:

• chr4-182689758-A-C
• rs9990730
• NM_001080477.4:c.2221+1407A>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.2221+1407A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.817 in 152,224 control chromosomes in the GnomAD database, including 50,825 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 0.82 (50825 hom., cov: 33)
• Consequence: TENM3 NM_001080477.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.258
• Publications: 1 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.892 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TENM3	NM_001080477.4	MANE Select	c.2221+1407A>C		intron	N/A	NP_001073946.1
	TENM3	NM_001415969.1		c.2221+1407A>C		intron	N/A	NP_001402898.1
	TENM3	NM_001415970.1		c.2221+1407A>C		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.2221+1407A>C		intron	N/A	ENSP00000424226.1
	TENM3	ENST00000502950.1	TSL:2	n.608+1407A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.817 AC: 124219 AN: 152106 Hom.: 50777 Cov.: 33

Gnomad AFR AF: 0.827

Gnomad AMI AF: 0.680

Gnomad AMR AF: 0.818

Gnomad ASJ AF: 0.828

Gnomad EAS AF: 0.914

Gnomad SAS AF: 0.822

Gnomad FIN AF: 0.809

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.806

Gnomad OTH AF: 0.780

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

GnomAD4 genome AF: 0.817 AC: 124326 AN: 152224 Hom.: 50825 Cov.: 33 AF XY: 0.817 AC XY: 60800 AN XY: 74412

African (AFR) AF: 0.828 AC: 34368 AN: 41532

American (AMR) AF: 0.819 AC: 12530 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.828 AC: 2871 AN: 3468

East Asian (EAS) AF: 0.913 AC: 4719 AN: 5166

South Asian (SAS) AF: 0.821 AC: 3963 AN: 4828

European-Finnish (FIN) AF: 0.809 AC: 8565 AN: 10588

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.806 AC: 54814 AN: 68018

Other (OTH) AF: 0.784 AC: 1655 AN: 2112

Alfa AF: 0.813 Hom.: 34694

Bravo AF: 0.817

Asia WGS AF: 0.874 AC: 3039 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.3
DANN	Benign	0.36
PhyloP100		-0.26
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: rs9990730; hg19: chr4-183610911;