rs12641856

Positions:

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

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_017008385.2(TENM3):​c.-399-50775G>A 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: TENM3 XM_017008385.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07

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]

ENSG00000287948 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TENM3	XM_017008385.2	c.-399-50775G>A		intron_variant			XP_016863874.1
TENM3	XM_047415933.1	c.-399-50775G>A		intron_variant			XP_047271889.1
TENM3	XM_017008389.2	c.-399-50775G>A		intron_variant			XP_016863878.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000287948	ENST00000670601.1	n.125-2069C>T		intron_variant

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

Gnomad4 AFR AF: 0.0162

Gnomad4 AMR AF: 0.0493

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.0647

Gnomad4 SAS AF: 0.140

Gnomad4 FIN AF: 0.0856

Gnomad4 NFE AF: 0.0862

Gnomad4 OTH AF: 0.0742

Alfa AF: 0.0646 Hom.: 178

Bravo AF: 0.0592

Asia WGS AF: 0.0980 AC: 340 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12641856; hg19: chr4-182609865;