rs12641856

Variant names:

• chr4-181688712-G-A
• rs12641856
• XM_017008385.2:c.-399-50775G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-181688712-G-A
• chr4-181688712-G-C

Variant summary

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

The ENST00000670601.1(ENSG00000287948):​n.125-2069C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0655 in 152,286 control chromosomes in the GnomAD database, including 448 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 0.066 (448 hom., cov: 33)
• Consequence: ENSG00000287948 ENST00000670601.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07
• Publications: 6 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

ENSG00000287948 (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 (SAS) allele frequency at 95% confidence interval = 0.131 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

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
	ENSG00000287948	ENST00000670601.1		n.125-2069C>T		intron	N/A
	ENSG00000299420	ENST00000763321.1		n.247-50775G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0656 AC: 9977 AN: 152168 Hom.: 447 Cov.: 33

Gnomad AFR AF: 0.0163

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.0494

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.0648

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.0856

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0862

Gnomad OTH AF: 0.0745

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

GnomAD4 genome AF: 0.0655 AC: 9982 AN: 152286 Hom.: 448 Cov.: 33 AF XY: 0.0666 AC XY: 4957 AN XY: 74444

African (AFR) AF: 0.0162 AC: 673 AN: 41590

American (AMR) AF: 0.0493 AC: 754 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 473 AN: 3470

East Asian (EAS) AF: 0.0647 AC: 334 AN: 5160

South Asian (SAS) AF: 0.140 AC: 677 AN: 4830

European-Finnish (FIN) AF: 0.0856 AC: 909 AN: 10616

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0862 AC: 5866 AN: 68016

Other (OTH) AF: 0.0742 AC: 157 AN: 2116

Alfa AF: 0.0632 Hom.: 350

Bravo AF: 0.0592

Asia WGS AF: 0.0980 AC: 340 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	8.7
DANN	Benign	0.62
PhyloP100		1.1

Splicing

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

Other links and lift over

dbSNP: rs12641856; hg19: chr4-182609865;