rs9990730

Positions:

• chr4-182689758-A-C
• chr4-182689758-A-T

Variant summary

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

The NM_001080477.4(TENM3):​c.2221+1407A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.817 in 152,224 control chromosomes in the GnomAD database, including 50,825 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 0.82 (50825 hom., cov: 33)
• Consequence: TENM3 NM_001080477.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.258

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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.892 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TENM3	NM_001080477.4	c.2221+1407A>C		intron_variant		ENST00000511685.6	NP_001073946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TENM3	ENST00000511685.6	c.2221+1407A>C		intron_variant		5	NM_001080477.4	ENSP00000424226	P1
TENM3	ENST00000502950.1	n.608+1407A>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.817 AC: 124219 AN: 152106 Hom.: 50777 Cov.: 33

Gnomad AFR AF: 0.827

Gnomad AMI AF: 0.680

Gnomad AMR AF: 0.818

Gnomad ASJ AF: 0.828

Gnomad EAS AF: 0.914

Gnomad SAS AF: 0.822

Gnomad FIN AF: 0.809

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.806

Gnomad OTH AF: 0.780

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

GnomAD4 genome AF: 0.817 AC: 124326 AN: 152224 Hom.: 50825 Cov.: 33 AF XY: 0.817 AC XY: 60800 AN XY: 74412

Gnomad4 AFR AF: 0.828

Gnomad4 AMR AF: 0.819

Gnomad4 ASJ AF: 0.828

Gnomad4 EAS AF: 0.913

Gnomad4 SAS AF: 0.821

Gnomad4 FIN AF: 0.809

Gnomad4 NFE AF: 0.806

Gnomad4 OTH AF: 0.784

Alfa AF: 0.813 Hom.: 23572

Bravo AF: 0.817

Asia WGS AF: 0.874 AC: 3039 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.3
DANN	Benign	0.36

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: rs9990730; hg19: chr4-183610911;