rs10520528

Variant names:

• chr4-182339448-T-G
• rs10520528
• NM_001080477.4:c.233-7203T>G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001080477.4(TENM3):​c.233-7203T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 152,016 control chromosomes in the GnomAD database, including 18,382 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 0.48 (18382 hom., cov: 32)
• Consequence: TENM3 NM_001080477.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.42

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM3	NM_001080477.4	c.233-7203T>G		intron_variant	Intron 2 of 27	ENST00000511685.6	NP_001073946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TENM3	ENST00000511685.6	c.233-7203T>G		intron_variant	Intron 2 of 27	5	NM_001080477.4	ENSP00000424226.1
TENM3	ENST00000513201.1	n.483-7203T>G		intron_variant	Intron 2 of 3	1
TENM3	ENST00000512480.5	c.233-7203T>G		intron_variant	Intron 2 of 2	3		ENSP00000421320.1

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73621 AN: 151898 Hom.: 18370 Cov.: 32

Gnomad AFR AF: 0.570

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.608

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.496

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.484

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

GnomAD4 genome AF: 0.485 AC: 73670 AN: 152016 Hom.: 18382 Cov.: 32 AF XY: 0.485 AC XY: 36051 AN XY: 74304

Gnomad4 AFR AF: 0.569

Gnomad4 AMR AF: 0.608

Gnomad4 ASJ AF: 0.363

Gnomad4 EAS AF: 0.496

Gnomad4 SAS AF: 0.507

Gnomad4 FIN AF: 0.421

Gnomad4 NFE AF: 0.421

Gnomad4 OTH AF: 0.482

Alfa AF: 0.444 Hom.: 20344

Bravo AF: 0.503

Asia WGS AF: 0.516 AC: 1792 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	18
DANN	Benign	0.83

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: rs10520528; hg19: chr4-183260601;