chr4-181478542-G-A

Variant names:

• chr4-181478542-G-A
• rs7672826
• XM_017008385.2:c.-400+30770G>A

Variant summary

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

The ENST00000812632.1(ENSG00000305728):​n.301-2513C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 151,918 control chromosomes in the GnomAD database, including 10,696 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 0.37 (10696 hom., cov: 32)
• Consequence: ENSG00000305728 ENST00000812632.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.702
• Publications: 21 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

ENSG00000305728 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000812632.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000305728	ENST00000812632.1		n.301-2513C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55679 AN: 151800 Hom.: 10671 Cov.: 32

Gnomad AFR AF: 0.485

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.358

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

GnomAD4 genome AF: 0.367 AC: 55750 AN: 151918 Hom.: 10696 Cov.: 32 AF XY: 0.366 AC XY: 27202 AN XY: 74248

African (AFR) AF: 0.486 AC: 20123 AN: 41424

American (AMR) AF: 0.364 AC: 5552 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 1198 AN: 3468

East Asian (EAS) AF: 0.323 AC: 1667 AN: 5164

South Asian (SAS) AF: 0.376 AC: 1813 AN: 4816

European-Finnish (FIN) AF: 0.249 AC: 2615 AN: 10522

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.317 AC: 21530 AN: 67958

Other (OTH) AF: 0.357 AC: 753 AN: 2112

Alfa AF: 0.341 Hom.: 22657

Bravo AF: 0.380

Asia WGS AF: 0.343 AC: 1192 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.7
DANN	Benign	0.69
PhyloP100		0.70

Splicing

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

Other links and lift over

dbSNP: rs7672826; hg19: chr4-182399695;