4-182556176-G-A

Position:

• chr4-182556176-G-A

Variant summary

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

The NM_001080477.4(TENM3):​c.512-44748G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 152,022 control chromosomes in the GnomAD database, including 12,910 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 0.39 (12910 hom., cov: 32)
• Consequence: TENM3 NM_001080477.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.66

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=-0.67).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.541 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TENM3	NM_001080477.4	c.512-44748G>A		intron_variant		ENST00000511685.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TENM3	ENST00000511685.6	c.512-44748G>A		intron_variant		5	NM_001080477.4	P1
TENM3	ENST00000510504.1	c.86-44748G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.391 AC: 59430 AN: 151906 Hom.: 12909 Cov.: 32

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.434

Gnomad EAS AF: 0.558

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.587

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.410

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

GnomAD4 genome AF: 0.391 AC: 59448 AN: 152022 Hom.: 12910 Cov.: 32 AF XY: 0.395 AC XY: 29350 AN XY: 74292

Gnomad4 AFR AF: 0.206

Gnomad4 AMR AF: 0.365

Gnomad4 ASJ AF: 0.434

Gnomad4 EAS AF: 0.558

Gnomad4 SAS AF: 0.403

Gnomad4 FIN AF: 0.587

Gnomad4 NFE AF: 0.464

Gnomad4 OTH AF: 0.412

Alfa AF: 0.452 Hom.: 26510

Bravo AF: 0.370

Asia WGS AF: 0.468 AC: 1623 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	2.0
DANN	Benign	0.39

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: rs10013166; hg19: chr4-183477329;