4-182638272-T-C

Variant names:

• chr4-182638272-T-C
• rs4507403
• NM_001080477.4:c.988+9383T>C

Variant summary

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

The NM_001080477.4(TENM3):​c.988+9383T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 152,026 control chromosomes in the GnomAD database, including 21,515 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 0.53 (21515 hom., cov: 32)
• Consequence: TENM3 NM_001080477.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.77
• Publications: 2 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM3	NM_001080477.4	c.988+9383T>C		intron_variant	Intron 5 of 27	ENST00000511685.6	NP_001073946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TENM3	ENST00000511685.6	c.988+9383T>C		intron_variant	Intron 5 of 27	5	NM_001080477.4	ENSP00000424226.1

Frequencies

GnomAD3 genomes AF: 0.528 AC: 80202 AN: 151908 Hom.: 21496 Cov.: 32

Gnomad AFR AF: 0.515

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.647

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.701

Gnomad SAS AF: 0.512

Gnomad FIN AF: 0.555

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.534

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

GnomAD4 genome AF: 0.528 AC: 80253 AN: 152026 Hom.: 21515 Cov.: 32 AF XY: 0.532 AC XY: 39551 AN XY: 74302

African (AFR) AF: 0.515 AC: 21342 AN: 41466

American (AMR) AF: 0.647 AC: 9888 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.548 AC: 1903 AN: 3472

East Asian (EAS) AF: 0.702 AC: 3623 AN: 5164

South Asian (SAS) AF: 0.512 AC: 2464 AN: 4814

European-Finnish (FIN) AF: 0.555 AC: 5852 AN: 10544

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.495 AC: 33625 AN: 67976

Other (OTH) AF: 0.532 AC: 1123 AN: 2112

Alfa AF: 0.503 Hom.: 38434

Bravo AF: 0.536

Asia WGS AF: 0.594 AC: 2062 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.2
DANN	Benign	0.73
PhyloP100		1.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs4507403; hg19: chr4-183559425;