rs9992452

Variant names:

• chr4-182596907-A-G
• rs9992452
• NM_001080477.4:c.512-4017A>G

Your query was ambiguous. Multiple possible variants found:

• chr4-182596907-A-G
• chr4-182596907-A-T

Variant summary

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

The NM_001080477.4(TENM3):​c.512-4017A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 152,014 control chromosomes in the GnomAD database, including 4,051 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 0.21 (4051 hom., cov: 32)
• Consequence: TENM3 NM_001080477.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.151
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM3	NM_001080477.4	c.512-4017A>G		intron_variant	Intron 3 of 27	ENST00000511685.6	NP_001073946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TENM3	ENST00000511685.6	c.512-4017A>G		intron_variant	Intron 3 of 27	5	NM_001080477.4	ENSP00000424226.1
TENM3	ENST00000510504.1	c.86-4017A>G		intron_variant	Intron 1 of 2	3		ENSP00000426914.1

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32218 AN: 151898 Hom.: 4050 Cov.: 32

Gnomad AFR AF: 0.353

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.193

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

GnomAD4 genome AF: 0.212 AC: 32227 AN: 152014 Hom.: 4051 Cov.: 32 AF XY: 0.208 AC XY: 15460 AN XY: 74284

African (AFR) AF: 0.353 AC: 14619 AN: 41434

American (AMR) AF: 0.133 AC: 2037 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 684 AN: 3468

East Asian (EAS) AF: 0.182 AC: 939 AN: 5146

South Asian (SAS) AF: 0.216 AC: 1039 AN: 4810

European-Finnish (FIN) AF: 0.108 AC: 1141 AN: 10568

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.164 AC: 11139 AN: 67994

Other (OTH) AF: 0.189 AC: 397 AN: 2104

Alfa AF: 0.185 Hom.: 5365

Bravo AF: 0.218

Asia WGS AF: 0.192 AC: 668 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.52
PhyloP100		-0.15
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: rs9992452; hg19: chr4-183518060;