rs4861977

Variant names:

• chr4-181512085-A-G
• rs4861977
• XM_017008385.2:c.-400+64313A>G

Variant summary

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

The XM_017008385.2(TENM3):​c.-400+64313A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 151,944 control chromosomes in the GnomAD database, including 2,175 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 0.15 (2175 hom., cov: 31)
• Consequence: TENM3 XM_017008385.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.915
• Publications: 1 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: 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM3	XM_017008385.2	c.-400+64313A>G		intron_variant	Intron 1 of 32		XP_016863874.1
TENM3	XM_017008389.2	c.-400+64313A>G		intron_variant	Intron 1 of 32		XP_016863878.1
TENM3	XM_017008390.2	c.-400+64313A>G		intron_variant	Intron 1 of 31		XP_016863879.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23156 AN: 151824 Hom.: 2168 Cov.: 31

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.0857

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.100

Gnomad OTH AF: 0.155

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

GnomAD4 genome AF: 0.153 AC: 23187 AN: 151944 Hom.: 2175 Cov.: 31 AF XY: 0.159 AC XY: 11819 AN XY: 74258

African (AFR) AF: 0.232 AC: 9592 AN: 41432

American (AMR) AF: 0.0855 AC: 1304 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 405 AN: 3472

East Asian (EAS) AF: 0.263 AC: 1351 AN: 5142

South Asian (SAS) AF: 0.283 AC: 1357 AN: 4792

European-Finnish (FIN) AF: 0.179 AC: 1891 AN: 10572

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.100 AC: 6824 AN: 67960

Other (OTH) AF: 0.156 AC: 328 AN: 2108

Alfa AF: 0.118 Hom.: 5381

Bravo AF: 0.146

Asia WGS AF: 0.272 AC: 943 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.11
DANN	Benign	0.59
PhyloP100		-0.92

Splicing

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

Other links and lift over

dbSNP: rs4861977; hg19: chr4-182433238;