chr4-182554781-A-C

Variant names:

• chr4-182554781-A-C
• rs13144500
• NM_001080477.4:c.512-46143A>C

Variant summary

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

The NM_001080477.4(TENM3):​c.512-46143A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,218 control chromosomes in the GnomAD database, including 1,408 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 0.12 (1408 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM3	NM_001080477.4	c.512-46143A>C		intron_variant	Intron 3 of 27	ENST00000511685.6	NP_001073946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TENM3	ENST00000511685.6	c.512-46143A>C		intron_variant	Intron 3 of 27	5	NM_001080477.4	ENSP00000424226.1
TENM3	ENST00000510504.1	c.86-46143A>C		intron_variant	Intron 1 of 2	3		ENSP00000426914.1

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18472 AN: 152100 Hom.: 1411 Cov.: 32

Gnomad AFR AF: 0.0320

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.121 AC: 18466 AN: 152218 Hom.: 1408 Cov.: 32 AF XY: 0.124 AC XY: 9200 AN XY: 74408

Gnomad4 AFR AF: 0.0319

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.146

Gnomad4 EAS AF: 0.224

Gnomad4 SAS AF: 0.192

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.154

Gnomad4 OTH AF: 0.125

Alfa AF: 0.145 Hom.: 2101

Bravo AF: 0.112

Asia WGS AF: 0.205 AC: 709 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.16
DANN	Benign	0.50

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: rs13144500; hg19: chr4-183475934;