chr4-182323716-C-T

Position:

• chr4-182323716-C-T

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.-75-230C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 151,932 control chromosomes in the GnomAD database, including 9,767 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.34 (9767 hom., cov: 32)
• Consequence: TENM3 NM_001080477.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.24

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=-0.95).
• BP6: Variant 4-182323716-C-T is Benign according to our data. Variant chr4-182323716-C-T is described in ClinVar as [Benign]. Clinvar id is 1280400.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TENM3	NM_001080477.4	c.-75-230C>T		intron_variant		ENST00000511685.6	NP_001073946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TENM3	ENST00000511685.6	c.-75-230C>T		intron_variant		5	NM_001080477.4	ENSP00000424226	P1
TENM3	ENST00000513201.1	n.176-230C>T		intron_variant, non_coding_transcript_variant		1
TENM3	ENST00000512480.5	c.-75-230C>T		intron_variant		3		ENSP00000421320

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51087 AN: 151812 Hom.: 9728 Cov.: 32

Gnomad AFR AF: 0.525

Gnomad AMI AF: 0.339

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.324

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

GnomAD4 genome AF: 0.337 AC: 51175 AN: 151932 Hom.: 9767 Cov.: 32 AF XY: 0.332 AC XY: 24637 AN XY: 74258

Gnomad4 AFR AF: 0.526

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.304

Gnomad4 EAS AF: 0.163

Gnomad4 SAS AF: 0.147

Gnomad4 FIN AF: 0.296

Gnomad4 NFE AF: 0.281

Gnomad4 OTH AF: 0.321

Alfa AF: 0.305 Hom.: 1525

Bravo AF: 0.339

Asia WGS AF: 0.191 AC: 665 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 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.016
DANN	Benign	0.70

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: rs6828445; hg19: chr4-183244869;