4-182346337-T-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001080477.4(TENM3):c.233-314T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.937 in 152,146 control chromosomes in the GnomAD database, including 67,332 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.94 (67332 hom., cov: 30)
• Consequence: TENM3 NM_001080477.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.171

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 4-182346337-T-A is Benign according to our data. Variant chr4-182346337-T-A is described in ClinVar as [Benign]. Clinvar id is 1263794.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.987 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TENM3	NM_001080477.4	c.233-314T>A		intron_variant		ENST00000511685.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TENM3	ENST00000511685.6	c.233-314T>A		intron_variant		5	NM_001080477.4	P1
TENM3	ENST00000513201.1	n.483-314T>A		intron_variant, non_coding_transcript_variant		1
TENM3	ENST00000512480.5	c.233-314T>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.938 AC: 142535 AN: 152028 Hom.: 67305 Cov.: 30

Gnomad AFR AF: 0.810

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.967

Gnomad ASJ AF: 0.919

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.955

Gnomad FIN AF: 0.997

Gnomad MID AF: 0.956

Gnomad NFE AF: 0.993

Gnomad OTH AF: 0.950

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

GnomAD4 genome AF: 0.937 AC: 142613 AN: 152146 Hom.: 67332 Cov.: 30 AF XY: 0.938 AC XY: 69781 AN XY: 74374

Gnomad4 AFR AF: 0.809

Gnomad4 AMR AF: 0.967

Gnomad4 ASJ AF: 0.919

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.955

Gnomad4 FIN AF: 0.997

Gnomad4 NFE AF: 0.993

Gnomad4 OTH AF: 0.950

Alfa AF: 0.967 Hom.: 8324

Bravo AF: 0.930

Asia WGS AF: 0.969 AC: 3369 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	3.0
Dann	Benign	0.60

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: rs6841633; hg19: chr4-183267490;