rs10000076

chr4-182367207-T-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+20278T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.96 in 152,268 control chromosomes in the GnomAD database, including 70,221 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 0.96 (70221 hom., cov: 32)
• Consequence: TENM3 NM_001080477.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.39

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.981 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TENM3	NM_001080477.4	c.511+20278T>G		intron_variant		ENST00000511685.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TENM3	ENST00000511685.6	c.511+20278T>G		intron_variant		5	NM_001080477.4	P1

Frequencies

GnomAD3 genomes AF: 0.960 AC: 146014 AN: 152150 Hom.: 70169 Cov.: 32

Gnomad AFR AF: 0.909

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.973

Gnomad ASJ AF: 0.904

Gnomad EAS AF: 0.945

Gnomad SAS AF: 0.952

Gnomad FIN AF: 0.989

Gnomad MID AF: 0.968

Gnomad NFE AF: 0.987

Gnomad OTH AF: 0.960

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

GnomAD4 genome AF: 0.960 AC: 146124 AN: 152268 Hom.: 70221 Cov.: 32 AF XY: 0.959 AC XY: 71420 AN XY: 74454

Gnomad4 AFR AF: 0.909

Gnomad4 AMR AF: 0.973

Gnomad4 ASJ AF: 0.904

Gnomad4 EAS AF: 0.945

Gnomad4 SAS AF: 0.951

Gnomad4 FIN AF: 0.989

Gnomad4 NFE AF: 0.987

Gnomad4 OTH AF: 0.960

Alfa AF: 0.976 Hom.: 14699

Bravo AF: 0.956

Asia WGS AF: 0.959 AC: 3335 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.099
Dann	Benign	0.28

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: rs10000076; hg19: chr4-183288360;