rs4862046

Positions:

• chr4-182379461-A-G

Variant summary

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

The NM_001080477.4(TENM3):​c.511+32532A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.886 in 152,194 control chromosomes in the GnomAD database, including 60,123 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 0.89 (60123 hom., cov: 32)
• Consequence: TENM3 NM_001080477.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0660

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.903 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TENM3	NM_001080477.4	c.511+32532A>G		intron_variant		ENST00000511685.6	NP_001073946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TENM3	ENST00000511685.6	c.511+32532A>G		intron_variant		5	NM_001080477.4	ENSP00000424226.1

Frequencies

GnomAD3 genomes AF: 0.886 AC: 134759 AN: 152076 Hom.: 60085 Cov.: 32

Gnomad AFR AF: 0.910

Gnomad AMI AF: 0.976

Gnomad AMR AF: 0.840

Gnomad ASJ AF: 0.894

Gnomad EAS AF: 0.582

Gnomad SAS AF: 0.855

Gnomad FIN AF: 0.876

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.907

Gnomad OTH AF: 0.876

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

GnomAD4 genome AF: 0.886 AC: 134846 AN: 152194 Hom.: 60123 Cov.: 32 AF XY: 0.881 AC XY: 65574 AN XY: 74406

Gnomad4 AFR AF: 0.910

Gnomad4 AMR AF: 0.840

Gnomad4 ASJ AF: 0.894

Gnomad4 EAS AF: 0.582

Gnomad4 SAS AF: 0.854

Gnomad4 FIN AF: 0.876

Gnomad4 NFE AF: 0.907

Gnomad4 OTH AF: 0.870

Alfa AF: 0.900 Hom.: 10524

Bravo AF: 0.883

Asia WGS AF: 0.700 AC: 2435 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.0
DANN	Benign	0.63

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: rs4862046; hg19: chr4-183300614;