chr4-182216245-T-C

Variant names:

• chr4-182216245-T-C
• rs2726807
• ENST00000513201.1:n.175+72084T>C

Variant summary

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

The NM_001415969.1(TENM3):​c.-76+72084T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 152,070 control chromosomes in the GnomAD database, including 25,262 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 0.57 (25262 hom., cov: 33)
• Consequence: TENM3 NM_001415969.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.224
• Publications: 8 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

LOC105377572 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001415969.1. 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
	TENM3	NM_001415969.1		c.-76+72084T>C		intron	N/A	NP_001402898.1
	TENM3	NM_001415970.1		c.-76+71491T>C		intron	N/A	NP_001402899.1
	TENM3	NM_001415968.1		c.-76+71491T>C		intron	N/A	NP_001402897.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TENM3	ENST00000513201.1	TSL:1	n.175+72084T>C		intron	N/A
	TENM3	ENST00000851042.1		c.-76+72084T>C		intron	N/A	ENSP00000521111.1
	TENM3	ENST00000851043.1		c.-76+71491T>C		intron	N/A	ENSP00000521112.1

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86636 AN: 151952 Hom.: 25255 Cov.: 33

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.530

Gnomad AMR AF: 0.618

Gnomad ASJ AF: 0.605

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.562

Gnomad FIN AF: 0.604

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.639

Gnomad OTH AF: 0.606

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

GnomAD4 genome AF: 0.570 AC: 86677 AN: 152070 Hom.: 25262 Cov.: 33 AF XY: 0.567 AC XY: 42191 AN XY: 74356

African (AFR) AF: 0.452 AC: 18738 AN: 41462

American (AMR) AF: 0.618 AC: 9445 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.605 AC: 2097 AN: 3468

East Asian (EAS) AF: 0.381 AC: 1963 AN: 5154

South Asian (SAS) AF: 0.562 AC: 2711 AN: 4820

European-Finnish (FIN) AF: 0.604 AC: 6391 AN: 10580

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.638 AC: 43411 AN: 67990

Other (OTH) AF: 0.600 AC: 1269 AN: 2114

Alfa AF: 0.617 Hom.: 94941

Bravo AF: 0.564

Asia WGS AF: 0.460 AC: 1602 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.4
DANN	Benign	0.59
PhyloP100		-0.22

Splicing

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

Other links and lift over

dbSNP: rs2726807; hg19: chr4-183137398;