rs11724903

Variant names:

• chr4-182278992-A-G
• rs11724903
• NM_001080477.4:c.-76+35516A>G

Variant summary

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

The NM_001080477.4(TENM3):​c.-76+35516A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 152,144 control chromosomes in the GnomAD database, including 5,596 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 0.24 (5596 hom., cov: 32)
• Consequence: TENM3 NM_001080477.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM3	NM_001080477.4	c.-76+35516A>G		intron_variant	Intron 1 of 27	ENST00000511685.6	NP_001073946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TENM3	ENST00000511685.6	c.-76+35516A>G		intron_variant	Intron 1 of 27	5	NM_001080477.4	ENSP00000424226.1
TENM3	ENST00000513201.1	n.176-44954A>G		intron_variant	Intron 1 of 3	1
TENM3	ENST00000512480.5	c.-75-44954A>G		intron_variant	Intron 1 of 2	3		ENSP00000421320.1

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36375 AN: 152026 Hom.: 5574 Cov.: 32

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.0531

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.238

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

GnomAD4 genome AF: 0.240 AC: 36439 AN: 152144 Hom.: 5596 Cov.: 32 AF XY: 0.236 AC XY: 17573 AN XY: 74390

African (AFR) AF: 0.433 AC: 17967 AN: 41484

American (AMR) AF: 0.207 AC: 3162 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 644 AN: 3468

East Asian (EAS) AF: 0.0536 AC: 277 AN: 5168

South Asian (SAS) AF: 0.107 AC: 516 AN: 4818

European-Finnish (FIN) AF: 0.173 AC: 1836 AN: 10602

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.167 AC: 11370 AN: 68002

Other (OTH) AF: 0.236 AC: 497 AN: 2106

Alfa AF: 0.186 Hom.: 2324

Bravo AF: 0.253

Asia WGS AF: 0.124 AC: 432 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.20
DANN	Benign	0.38
PhyloP100		-2.0
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: rs11724903; hg19: chr4-183200145;