chr4-182346948-T-C

Variant names:

• chr4-182346948-T-C
• rs760777000
• NM_001080477.4:c.511+19T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001080477.4(TENM3):​c.511+19T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000709 in 1,409,578 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: TENM3 NM_001080477.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.239
• 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: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• microphthalmia, isolated, with coloboma

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.24).
• BP6: Variant 4-182346948-T-C is Benign according to our data. Variant chr4-182346948-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1966835.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM3	NM_001080477.4	c.511+19T>C		intron_variant	Intron 3 of 27	ENST00000511685.6	NP_001073946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TENM3	ENST00000511685.6	c.511+19T>C		intron_variant	Intron 3 of 27	5	NM_001080477.4	ENSP00000424226.1
TENM3	ENST00000513201.1	n.761+19T>C		intron_variant	Intron 3 of 3	1
TENM3	ENST00000512480.5	c.*19T>C		downstream_gene_variant		3		ENSP00000421320.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.09e-7 AC: 1 AN: 1409578 Hom.: 0 Cov.: 33 AF XY: 0.00000143 AC XY: 1 AN XY: 696890

African (AFR) AF: 0.00 AC: 0 AN: 32552

American (AMR) AF: 0.0000241 AC: 1 AN: 41532

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23462

East Asian (EAS) AF: 0.00 AC: 0 AN: 37472

South Asian (SAS) AF: 0.00 AC: 0 AN: 80626

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50356

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5398

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1080520

Other (OTH) AF: 0.00 AC: 0 AN: 57660

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 28, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
CADD	Benign	8.7
DANN	Benign	0.84
PhyloP100		0.24

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: rs760777000; hg19: chr4-183268101;