rs7697691

Variant names:

• chr4-181695804-G-A
• rs7697691
• ENST00000670601.1:n.124+4215C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-181695804-G-A
• chr4-181695804-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.124+4215C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.797 in 152,144 control chromosomes in the GnomAD database, including 48,582 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 0.80 (48582 hom., cov: 33)
• Consequence: ENSG00000287948 ENST00000670601.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.796
• Publications: 4 publications found

Genes affected

ENSG00000287948 (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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM3	XM_017008385.2	c.-399-43683G>A		intron_variant	Intron 1 of 32		XP_016863874.1
TENM3	XM_047415933.1	c.-399-43683G>A		intron_variant	Intron 1 of 32		XP_047271889.1
TENM3	XM_017008389.2	c.-399-43683G>A		intron_variant	Intron 1 of 32		XP_016863878.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000287948	ENST00000670601.1	n.124+4215C>T		intron_variant	Intron 1 of 1
ENSG00000299420	ENST00000763321.1	n.247-43683G>A		intron_variant	Intron 3 of 6

Frequencies

GnomAD3 genomes AF: 0.797 AC: 121221 AN: 152026 Hom.: 48533 Cov.: 33

Gnomad AFR AF: 0.738

Gnomad AMI AF: 0.790

Gnomad AMR AF: 0.881

Gnomad ASJ AF: 0.799

Gnomad EAS AF: 0.727

Gnomad SAS AF: 0.741

Gnomad FIN AF: 0.781

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.826

Gnomad OTH AF: 0.813

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

GnomAD4 genome AF: 0.797 AC: 121324 AN: 152144 Hom.: 48582 Cov.: 33 AF XY: 0.794 AC XY: 59075 AN XY: 74374

African (AFR) AF: 0.738 AC: 30626 AN: 41498

American (AMR) AF: 0.881 AC: 13481 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.799 AC: 2774 AN: 3472

East Asian (EAS) AF: 0.727 AC: 3757 AN: 5170

South Asian (SAS) AF: 0.740 AC: 3572 AN: 4826

European-Finnish (FIN) AF: 0.781 AC: 8246 AN: 10562

Middle Eastern (MID) AF: 0.840 AC: 247 AN: 294

European-Non Finnish (NFE) AF: 0.826 AC: 56192 AN: 68008

Other (OTH) AF: 0.810 AC: 1710 AN: 2110

Alfa AF: 0.811 Hom.: 8161

Bravo AF: 0.804

Asia WGS AF: 0.744 AC: 2589 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.083
DANN	Benign	0.56
PhyloP100		-0.80

Splicing

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

Other links and lift over

dbSNP: rs7697691; hg19: chr4-182616957;