4-182323716-C-T

Variant names:

• chr4-182323716-C-T
• rs6828445
• NM_001080477.4:c.-75-230C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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]

TENM3 Gene-Disease associations (from GenCC):

• microphthalmia, isolated, with coloboma 9

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, PanelApp Australia
• microphthalmia, isolated, with coloboma

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080477.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TENM3	NM_001080477.4	MANE Select	c.-75-230C>T		intron	N/A	NP_001073946.1	Q9P273
	TENM3	NM_001415969.1		c.-75-230C>T		intron	N/A	NP_001402898.1
	TENM3	NM_001415970.1		c.-75-230C>T		intron	N/A	NP_001402899.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TENM3	ENST00000511685.6	TSL:5 MANE Select	c.-75-230C>T		intron	N/A	ENSP00000424226.1	Q9P273
	TENM3	ENST00000513201.1	TSL:1	n.176-230C>T		intron	N/A
	TENM3	ENST00000851056.1		c.-75-230C>T		intron	N/A	ENSP00000521125.1

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

African (AFR) AF: 0.526 AC: 21768 AN: 41402

American (AMR) AF: 0.227 AC: 3472 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 1056 AN: 3470

East Asian (EAS) AF: 0.163 AC: 843 AN: 5162

South Asian (SAS) AF: 0.147 AC: 706 AN: 4818

European-Finnish (FIN) AF: 0.296 AC: 3112 AN: 10530

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.281 AC: 19130 AN: 67970

Other (OTH) AF: 0.321 AC: 676 AN: 2104

Alfa AF: 0.303 Hom.: 2529

Bravo AF: 0.339

Asia WGS AF: 0.191 AC: 665 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.016
DANN	Benign	0.70
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6828445; hg19: chr4-183244869;