4-181717360-A-G

Variant names:

• chr4-181717360-A-G
• rs6848193
• XM_017008385.2:c.-399-22127A>G

Variant summary

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

The ENST00000763321.1(ENSG00000299420):​n.247-22127A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.511 in 151,966 control chromosomes in the GnomAD database, including 20,467 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 0.51 (20467 hom., cov: 32)
• Consequence: ENSG00000299420 ENST00000763321.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.386
• Publications: 2 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, PanelApp Australia
• microphthalmia, isolated, with coloboma

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000299420 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000763321.1. 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
	ENSG00000299420	ENST00000763321.1		n.247-22127A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77673 AN: 151846 Hom.: 20452 Cov.: 32

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.622

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.620

Gnomad SAS AF: 0.515

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.555

Gnomad OTH AF: 0.538

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

GnomAD4 genome AF: 0.511 AC: 77723 AN: 151966 Hom.: 20467 Cov.: 32 AF XY: 0.513 AC XY: 38153 AN XY: 74308

African (AFR) AF: 0.373 AC: 15465 AN: 41444

American (AMR) AF: 0.622 AC: 9495 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 1735 AN: 3462

East Asian (EAS) AF: 0.619 AC: 3205 AN: 5174

South Asian (SAS) AF: 0.514 AC: 2475 AN: 4814

European-Finnish (FIN) AF: 0.576 AC: 6089 AN: 10574

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.555 AC: 37669 AN: 67916

Other (OTH) AF: 0.539 AC: 1140 AN: 2114

Alfa AF: 0.538 Hom.: 15342

Bravo AF: 0.510

Asia WGS AF: 0.549 AC: 1908 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	7.3
DANN	Benign	0.71
PhyloP100		0.39

Splicing

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

Other links and lift over

dbSNP: rs6848193; hg19: chr4-182638513;