rs6552560

Positions:

• chr4-182371476-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TENM3	NM_001080477.4	c.511+24547C>T		intron_variant		ENST00000511685.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TENM3	ENST00000511685.6	c.511+24547C>T		intron_variant		5	NM_001080477.4	P1

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

Gnomad4 AFR AF: 0.346

Gnomad4 AMR AF: 0.167

Gnomad4 ASJ AF: 0.144

Gnomad4 EAS AF: 0.00984

Gnomad4 SAS AF: 0.0662

Gnomad4 FIN AF: 0.185

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.197

Alfa AF: 0.192 Hom.: 4256

Bravo AF: 0.231

Asia WGS AF: 0.0680 AC: 236 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.099
DANN	Benign	0.32

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

Publications

LitVar

Other links and lift over

dbSNP: rs6552560; hg19: chr4-183292629;