chr4-181486725-T-C

Variant names:

• chr4-181486725-T-C
• rs17198973
• XM_017008385.2:c.-400+38953T>C

Variant summary

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

The ENST00000812632.1(ENSG00000305728):​n.300+1463A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 151,954 control chromosomes in the GnomAD database, including 20,989 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 0.52 (20989 hom., cov: 32)
• Consequence: ENSG00000305728 ENST00000812632.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0190
• 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, PanelApp Australia
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.587 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.300+1463A>G		intron	N/A
	ENSG00000305728	ENST00000812633.1		n.352-243A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78648 AN: 151838 Hom.: 20986 Cov.: 32

Gnomad AFR AF: 0.408

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.564

Gnomad EAS AF: 0.377

Gnomad SAS AF: 0.529

Gnomad FIN AF: 0.522

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.592

Gnomad OTH AF: 0.545

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

GnomAD4 genome AF: 0.518 AC: 78668 AN: 151954 Hom.: 20989 Cov.: 32 AF XY: 0.515 AC XY: 38250 AN XY: 74252

African (AFR) AF: 0.408 AC: 16900 AN: 41452

American (AMR) AF: 0.510 AC: 7796 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.564 AC: 1958 AN: 3470

East Asian (EAS) AF: 0.376 AC: 1938 AN: 5152

South Asian (SAS) AF: 0.529 AC: 2548 AN: 4816

European-Finnish (FIN) AF: 0.522 AC: 5512 AN: 10556

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.592 AC: 40232 AN: 67922

Other (OTH) AF: 0.542 AC: 1142 AN: 2108

Alfa AF: 0.564 Hom.: 6084

Bravo AF: 0.511

Asia WGS AF: 0.437 AC: 1518 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	14
DANN	Benign	0.40
PhyloP100		0.019

Splicing

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

Other links and lift over

dbSNP: rs17198973; hg19: chr4-182407878;