rs6552560

Variant names:

• chr4-182371476-C-T
• rs6552560
• NM_001080477.4:c.511+24547C>T

Variant summary

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

The NM_001080477.4(TENM3):​c.511+24547C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 152,018 control chromosomes in the GnomAD database, including 4,396 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 0.22 (4396 hom., cov: 32)
• Consequence: TENM3 NM_001080477.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.780
• Publications: 4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.342 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.511+24547C>T		intron	N/A	NP_001073946.1	Q9P273
	TENM3	NM_001415969.1		c.511+24547C>T		intron	N/A	NP_001402898.1
	TENM3	NM_001415970.1		c.511+24547C>T		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.511+24547C>T		intron	N/A	ENSP00000424226.1	Q9P273
	TENM3	ENST00000851056.1		c.511+24547C>T		intron	N/A	ENSP00000521125.1
	TENM3	ENST00000851057.1		c.511+24547C>T		intron	N/A	ENSP00000521126.1

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33700 AN: 151900 Hom.: 4384 Cov.: 32

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.00982

Gnomad SAS AF: 0.0666

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.222 AC: 33730 AN: 152018 Hom.: 4396 Cov.: 32 AF XY: 0.216 AC XY: 16044 AN XY: 74298

African (AFR) AF: 0.346 AC: 14349 AN: 41430

American (AMR) AF: 0.167 AC: 2554 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 500 AN: 3468

East Asian (EAS) AF: 0.00984 AC: 51 AN: 5182

South Asian (SAS) AF: 0.0662 AC: 319 AN: 4818

European-Finnish (FIN) AF: 0.185 AC: 1948 AN: 10552

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.195 AC: 13268 AN: 67990

Other (OTH) AF: 0.197 AC: 414 AN: 2104

Alfa AF: 0.198 Hom.: 6257

Bravo AF: 0.231

Asia WGS AF: 0.0680 AC: 236 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.099
DANN	Benign	0.32
PhyloP100		-0.78
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: rs6552560; hg19: chr4-183292629;