4-182766636-T-C

Position:

• chr4-182766636-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080477.4(TENM3):​c.4893-6836T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 152,064 control chromosomes in the GnomAD database, including 2,642 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 0.17 (2642 hom., cov: 32)
• Consequence: TENM3 NM_001080477.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0170

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]

LOC105377571 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TENM3	NM_001080477.4	c.4893-6836T>C		intron_variant		ENST00000511685.6	NP_001073946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TENM3	ENST00000511685.6	c.4893-6836T>C		intron_variant		5	NM_001080477.4	ENSP00000424226.1

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25899 AN: 151946 Hom.: 2630 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.0989

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.319

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.171 AC: 25940 AN: 152064 Hom.: 2642 Cov.: 32 AF XY: 0.180 AC XY: 13351 AN XY: 74310

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.255

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.319

Gnomad4 SAS AF: 0.191

Gnomad4 FIN AF: 0.291

Gnomad4 NFE AF: 0.145

Gnomad4 OTH AF: 0.160

Alfa AF: 0.153 Hom.: 1273

Bravo AF: 0.168

Asia WGS AF: 0.233 AC: 808 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	9.6
DANN	Benign	0.89

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: rs10017238; hg19: chr4-183687789;