rs955638

Variant names:

• chr4-182333508-A-G
• rs955638
• NM_001080477.4:c.232+9256A>G

Variant summary

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

The NM_001080477.4(TENM3):​c.232+9256A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 152,020 control chromosomes in the GnomAD database, including 6,071 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 0.27 (6071 hom., cov: 32)
• Consequence: TENM3 NM_001080477.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.590
• Publications: 6 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 (NFE) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM3	NM_001080477.4	c.232+9256A>G		intron_variant	Intron 2 of 27	ENST00000511685.6	NP_001073946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TENM3	ENST00000511685.6	c.232+9256A>G		intron_variant	Intron 2 of 27	5	NM_001080477.4	ENSP00000424226.1
TENM3	ENST00000513201.1	n.482+9256A>G		intron_variant	Intron 2 of 3	1
TENM3	ENST00000512480.5	c.232+9256A>G		intron_variant	Intron 2 of 2	3		ENSP00000421320.1

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41762 AN: 151898 Hom.: 6070 Cov.: 32

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.353

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.290

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.288

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

GnomAD4 genome AF: 0.275 AC: 41782 AN: 152020 Hom.: 6071 Cov.: 32 AF XY: 0.272 AC XY: 20230 AN XY: 74316

African (AFR) AF: 0.234 AC: 9714 AN: 41472

American (AMR) AF: 0.231 AC: 3534 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.360 AC: 1250 AN: 3472

East Asian (EAS) AF: 0.127 AC: 655 AN: 5170

South Asian (SAS) AF: 0.202 AC: 971 AN: 4818

European-Finnish (FIN) AF: 0.284 AC: 2996 AN: 10554

Middle Eastern (MID) AF: 0.274 AC: 79 AN: 288

European-Non Finnish (NFE) AF: 0.319 AC: 21658 AN: 67952

Other (OTH) AF: 0.287 AC: 604 AN: 2108

Alfa AF: 0.305 Hom.: 10632

Bravo AF: 0.272

Asia WGS AF: 0.145 AC: 503 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.8
DANN	Benign	0.38
PhyloP100		0.59
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: rs955638; hg19: chr4-183254661;