4-182346575-TAA-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001080477.4(TENM3):c.233-63_233-62del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 828,246 control chromosomes in the GnomAD database, including 490 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.044 (135 hom., cov: 0)
  • Exomes 𝑓: 0.15 (355 hom.)
• Consequence: TENM3 NM_001080477.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.110

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.

• BP6: Variant 4-182346575-TAA-T is Benign according to our data. Variant chr4-182346575-TAA-T is described in ClinVar as [Likely_benign]. Clinvar id is 1326030.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TENM3	NM_001080477.4	c.233-63_233-62del		intron_variant		ENST00000511685.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TENM3	ENST00000511685.6	c.233-63_233-62del		intron_variant		5	NM_001080477.4	P1
TENM3	ENST00000513201.1	n.483-63_483-62del		intron_variant, non_coding_transcript_variant		1
TENM3	ENST00000512480.5	c.233-63_233-62del		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0439 AC: 6424 AN: 146178 Hom.: 134 Cov.: 0

Gnomad AFR AF: 0.0376

Gnomad AMI AF: 0.00111

Gnomad AMR AF: 0.0640

Gnomad ASJ AF: 0.0459

Gnomad EAS AF: 0.0365

Gnomad SAS AF: 0.0519

Gnomad FIN AF: 0.0338

Gnomad MID AF: 0.0455

Gnomad NFE AF: 0.0449

Gnomad OTH AF: 0.0512

GnomAD4 exome AF: 0.146 AC: 99308 AN: 682010 Hom.: 355 AF XY: 0.146 AC XY: 49795 AN XY: 340190

Gnomad4 AFR exome AF: 0.103

Gnomad4 AMR exome AF: 0.186

Gnomad4 ASJ exome AF: 0.115

Gnomad4 EAS exome AF: 0.141

Gnomad4 SAS exome AF: 0.157

Gnomad4 FIN exome AF: 0.124

Gnomad4 NFE exome AF: 0.148

Gnomad4 OTH exome AF: 0.137

GnomAD4 genome AF: 0.0440 AC: 6437 AN: 146236 Hom.: 135 Cov.: 0 AF XY: 0.0441 AC XY: 3129 AN XY: 70968

Gnomad4 AFR AF: 0.0378

Gnomad4 AMR AF: 0.0639

Gnomad4 ASJ AF: 0.0459

Gnomad4 EAS AF: 0.0366

Gnomad4 SAS AF: 0.0521

Gnomad4 FIN AF: 0.0338

Gnomad4 NFE AF: 0.0450

Gnomad4 OTH AF: 0.0512

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 16, 2021

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Computational scores

Source: dbNSFP v4.3

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: rs33933747; hg19: chr4-183267728;