rs13340295

chr4-182728947-G-Achr4-182728947-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001080477.4(TENM3):c.2369-18G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0584 in 1,605,396 control chromosomes in the GnomAD database, including 3,474 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.081 (779 hom., cov: 32)
  • Exomes 𝑓: 0.056 (2695 hom.)
• Consequence: TENM3 NM_001080477.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.00600

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 4-182728947-G-A is Benign according to our data. Variant chr4-182728947-G-A is described in ClinVar as [Benign]. Clinvar id is 257348.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TENM3	NM_001080477.4	c.2369-18G>A		intron_variant		ENST00000511685.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TENM3	ENST00000511685.6	c.2369-18G>A		intron_variant		5	NM_001080477.4	P1
TENM3	ENST00000502950.1	n.756-18G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0813 AC: 12347 AN: 151794 Hom.: 774 Cov.: 32

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.0565

Gnomad ASJ AF: 0.0444

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.0418

Gnomad FIN AF: 0.0140

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0562

Gnomad OTH AF: 0.0755

GnomAD3 exomes AF: 0.0523 AC: 12883 AN: 246326 Hom.: 524 AF XY: 0.0515 AC XY: 6882 AN XY: 133584

Gnomad AFR exome AF: 0.174

Gnomad AMR exome AF: 0.0380

Gnomad ASJ exome AF: 0.0452

Gnomad EAS exome AF: 0.0000560

Gnomad SAS exome AF: 0.0448

Gnomad FIN exome AF: 0.0159

Gnomad NFE exome AF: 0.0577

Gnomad OTH exome AF: 0.0573

GnomAD4 exome AF: 0.0560 AC: 81338 AN: 1453492 Hom.: 2695 Cov.: 30 AF XY: 0.0553 AC XY: 39975 AN XY: 723070

Gnomad4 AFR exome AF: 0.169

Gnomad4 AMR exome AF: 0.0398

Gnomad4 ASJ exome AF: 0.0447

Gnomad4 EAS exome AF: 0.000152

Gnomad4 SAS exome AF: 0.0469

Gnomad4 FIN exome AF: 0.0173

Gnomad4 NFE exome AF: 0.0575

Gnomad4 OTH exome AF: 0.0624

GnomAD4 genome AF: 0.0814 AC: 12361 AN: 151904 Hom.: 779 Cov.: 32 AF XY: 0.0789 AC XY: 5856 AN XY: 74264

Gnomad4 AFR AF: 0.168

Gnomad4 AMR AF: 0.0564

Gnomad4 ASJ AF: 0.0444

Gnomad4 EAS AF: 0.000580

Gnomad4 SAS AF: 0.0410

Gnomad4 FIN AF: 0.0140

Gnomad4 NFE AF: 0.0562

Gnomad4 OTH AF: 0.0747

Alfa AF: 0.0655 Hom.: 374

Bravo AF: 0.0890

Asia WGS AF: 0.0340 AC: 118 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 01, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.66
Dann	Benign	0.26

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: rs13340295; hg19: chr4-183650100;