chr4-181478542-G-A

Position:

• chr4-181478542-G-A

Variant summary

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

The XM_017008385.2(TENM3):​c.-400+30770G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 151,918 control chromosomes in the GnomAD database, including 10,696 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 0.37 (10696 hom., cov: 32)
• Consequence: TENM3 XM_017008385.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.702

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TENM3	XM_017008385.2	c.-400+30770G>A		intron_variant			XP_016863874.1
TENM3	XM_017008389.2	c.-400+30770G>A		intron_variant			XP_016863878.1
TENM3	XM_017008390.2	c.-400+30770G>A		intron_variant			XP_016863879.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55679 AN: 151800 Hom.: 10671 Cov.: 32

Gnomad AFR AF: 0.485

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.358

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

GnomAD4 genome AF: 0.367 AC: 55750 AN: 151918 Hom.: 10696 Cov.: 32 AF XY: 0.366 AC XY: 27202 AN XY: 74248

Gnomad4 AFR AF: 0.486

Gnomad4 AMR AF: 0.364

Gnomad4 ASJ AF: 0.345

Gnomad4 EAS AF: 0.323

Gnomad4 SAS AF: 0.376

Gnomad4 FIN AF: 0.249

Gnomad4 NFE AF: 0.317

Gnomad4 OTH AF: 0.357

Alfa AF: 0.331 Hom.: 13824

Bravo AF: 0.380

Asia WGS AF: 0.343 AC: 1192 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.7
DANN	Benign	0.69

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7672826; hg19: chr4-182399695;