NM_001080477.4:c.233-314T>A

Variant names:

• chr4-182346337-T-A
• rs6841633
• NM_001080477.4:c.233-314T>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001080477.4(TENM3):​c.233-314T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.937 in 152,146 control chromosomes in the GnomAD database, including 67,332 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.94 (67332 hom., cov: 30)
• Consequence: TENM3 NM_001080477.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.171
• Publications: 0 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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 4-182346337-T-A is Benign according to our data. Variant chr4-182346337-T-A is described in ClinVar as Benign. ClinVar VariationId is 1263794.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.987 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080477.4. 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_001080477.4	MANE Select	c.233-314T>A		intron	N/A	NP_001073946.1	Q9P273
	TENM3	NM_001415969.1		c.233-314T>A		intron	N/A	NP_001402898.1
	TENM3	NM_001415970.1		c.233-314T>A		intron	N/A	NP_001402899.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TENM3	ENST00000511685.6	TSL:5 MANE Select	c.233-314T>A		intron	N/A	ENSP00000424226.1	Q9P273
	TENM3	ENST00000513201.1	TSL:1	n.483-314T>A		intron	N/A
	TENM3	ENST00000851056.1		c.233-314T>A		intron	N/A	ENSP00000521125.1

Frequencies

GnomAD3 genomes AF: 0.938 AC: 142535 AN: 152028 Hom.: 67305 Cov.: 30

Gnomad AFR AF: 0.810

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.967

Gnomad ASJ AF: 0.919

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.955

Gnomad FIN AF: 0.997

Gnomad MID AF: 0.956

Gnomad NFE AF: 0.993

Gnomad OTH AF: 0.950

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

GnomAD4 genome AF: 0.937 AC: 142613 AN: 152146 Hom.: 67332 Cov.: 30 AF XY: 0.938 AC XY: 69781 AN XY: 74374

African (AFR) AF: 0.809 AC: 33560 AN: 41458

American (AMR) AF: 0.967 AC: 14793 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.919 AC: 3190 AN: 3470

East Asian (EAS) AF: 0.999 AC: 5133 AN: 5136

South Asian (SAS) AF: 0.955 AC: 4601 AN: 4820

European-Finnish (FIN) AF: 0.997 AC: 10593 AN: 10620

Middle Eastern (MID) AF: 0.959 AC: 282 AN: 294

European-Non Finnish (NFE) AF: 0.993 AC: 67544 AN: 68026

Other (OTH) AF: 0.950 AC: 2005 AN: 2110

Alfa AF: 0.967 Hom.: 8324

Bravo AF: 0.930

Asia WGS AF: 0.969 AC: 3369 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.0
DANN	Benign	0.60
PhyloP100		0.17
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: rs6841633; hg19: chr4-183267490;