rs17071568

Variant names:

• chr4-181476379-G-A
• rs17071568
• ENST00000812632.1:n.301-350C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-181476379-G-A
• chr4-181476379-G-T

Variant summary

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

The ENST00000812632.1(ENSG00000305728):​n.301-350C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 151,770 control chromosomes in the GnomAD database, including 10,357 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 0.36 (10357 hom., cov: 31)
• Consequence: ENSG00000305728 ENST00000812632.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.231
• Publications: 1 publications found

Genes affected

ENSG00000305728 (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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM3	XM_017008385.2	c.-400+28607G>A		intron_variant	Intron 1 of 32		XP_016863874.1
TENM3	XM_017008389.2	c.-400+28607G>A		intron_variant	Intron 1 of 32		XP_016863878.1
TENM3	XM_017008390.2	c.-400+28607G>A		intron_variant	Intron 1 of 31		XP_016863879.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000305728	ENST00000812632.1	n.301-350C>T		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54809 AN: 151650 Hom.: 10337 Cov.: 31

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.455

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.353

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

GnomAD4 genome AF: 0.362 AC: 54870 AN: 151770 Hom.: 10357 Cov.: 31 AF XY: 0.360 AC XY: 26704 AN XY: 74156

African (AFR) AF: 0.473 AC: 19549 AN: 41328

American (AMR) AF: 0.361 AC: 5502 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 1197 AN: 3470

East Asian (EAS) AF: 0.316 AC: 1623 AN: 5134

South Asian (SAS) AF: 0.346 AC: 1662 AN: 4804

European-Finnish (FIN) AF: 0.250 AC: 2632 AN: 10520

Middle Eastern (MID) AF: 0.452 AC: 132 AN: 292

European-Non Finnish (NFE) AF: 0.316 AC: 21460 AN: 67944

Other (OTH) AF: 0.352 AC: 745 AN: 2116

Alfa AF: 0.309 Hom.: 3412

Bravo AF: 0.374

Asia WGS AF: 0.328 AC: 1142 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.079
DANN	Benign	0.76
PhyloP100		-0.23

Splicing

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

Other links and lift over

dbSNP: rs17071568; hg19: chr4-182397532;