rs12500335

chr4-182786628-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.5305-2465A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 151,692 control chromosomes in the GnomAD database, including 1,079 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 0.10 (1079 hom., cov: 30)
• Consequence: TENM3 NM_001080477.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TENM3	NM_001080477.4	c.5305-2465A>G		intron_variant		ENST00000511685.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TENM3	ENST00000511685.6	c.5305-2465A>G		intron_variant		5	NM_001080477.4	P1

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15550 AN: 151584 Hom.: 1079 Cov.: 30

Gnomad AFR AF: 0.0240

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.0994

Gnomad EAS AF: 0.0872

Gnomad SAS AF: 0.0962

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.0796

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.103 AC: 15553 AN: 151692 Hom.: 1079 Cov.: 30 AF XY: 0.106 AC XY: 7843 AN XY: 74080

Gnomad4 AFR AF: 0.0239

Gnomad4 AMR AF: 0.159

Gnomad4 ASJ AF: 0.0994

Gnomad4 EAS AF: 0.0876

Gnomad4 SAS AF: 0.0967

Gnomad4 FIN AF: 0.169

Gnomad4 NFE AF: 0.130

Gnomad4 OTH AF: 0.102

Alfa AF: 0.116 Hom.: 1293

Bravo AF: 0.0942

Asia WGS AF: 0.0890 AC: 311 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.32
Dann	Benign	0.25

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: rs12500335; hg19: chr4-183707781;