ENST00000670601.1:n.124+948A>C

Variant names:

• chr4-181699071-T-G
• rs726856
• ENST00000670601.1:n.124+948A>C

Variant summary

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

The ENST00000670601.1(ENSG00000287948):​n.124+948A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 151,828 control chromosomes in the GnomAD database, including 18,204 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 0.47 (18204 hom., cov: 31)
• Consequence: ENSG00000287948 ENST00000670601.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0240
• Publications: 1 publications found

Genes affected

ENSG00000287948 (HGNC:):

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000670601.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000287948	ENST00000670601.1		n.124+948A>C		intron	N/A
	ENSG00000299420	ENST00000763321.1		n.247-40416T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.475 AC: 72031 AN: 151710 Hom.: 18187 Cov.: 31

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.437

Gnomad AMR AF: 0.404

Gnomad ASJ AF: 0.513

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.529

Gnomad FIN AF: 0.616

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.475

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

GnomAD4 genome AF: 0.475 AC: 72092 AN: 151828 Hom.: 18204 Cov.: 31 AF XY: 0.473 AC XY: 35129 AN XY: 74214

African (AFR) AF: 0.338 AC: 13973 AN: 41390

American (AMR) AF: 0.404 AC: 6155 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.513 AC: 1781 AN: 3472

East Asian (EAS) AF: 0.194 AC: 999 AN: 5156

South Asian (SAS) AF: 0.529 AC: 2540 AN: 4806

European-Finnish (FIN) AF: 0.616 AC: 6504 AN: 10550

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.568 AC: 38563 AN: 67894

Other (OTH) AF: 0.478 AC: 1007 AN: 2106

Alfa AF: 0.544 Hom.: 11820

Bravo AF: 0.448

Asia WGS AF: 0.396 AC: 1377 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.18
DANN	Benign	0.63
PhyloP100		0.024

Splicing

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

Other links and lift over

dbSNP: rs726856; hg19: chr4-182620224;