chr4-182346820-T-C

Variant names:

• chr4-182346820-T-C
• rs759894262
• NM_001080477.4:c.402T>C

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001080477.4(TENM3):​c.402T>C​(p.Leu134Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000164 in 1,461,288 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: 0.000016 (0 hom.)
• Consequence: TENM3 NM_001080477.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0950
• 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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 4-182346820-T-C is Benign according to our data. Variant chr4-182346820-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 754367.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.095 with no splicing effect.

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.402T>C	p.Leu134Leu	synonymous	Exon 3 of 28	NP_001073946.1	Q9P273
	TENM3	NM_001415969.1		c.402T>C	p.Leu134Leu	synonymous	Exon 3 of 29	NP_001402898.1
	TENM3	NM_001415970.1		c.402T>C	p.Leu134Leu	synonymous	Exon 3 of 29	NP_001402899.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TENM3	ENST00000511685.6	TSL:5 MANE Select	c.402T>C	p.Leu134Leu	synonymous	Exon 3 of 28	ENSP00000424226.1	Q9P273
	TENM3	ENST00000513201.1	TSL:1	n.652T>C		non_coding_transcript_exon	Exon 3 of 4
	TENM3	ENST00000851056.1		c.402T>C	p.Leu134Leu	synonymous	Exon 3 of 31	ENSP00000521125.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000806 AC: 20 AN: 248000 AF XY: 0.0000520

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000524

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000558

Gnomad FIN exome AF: 0.0000465

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000164 AC: 24 AN: 1461288 Hom.: 0 Cov.: 33 AF XY: 0.0000124 AC XY: 9 AN XY: 726884

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.000403 AC: 18 AN: 44662

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86148

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53380

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111704

Other (OTH) AF: 0.00 AC: 0 AN: 60360

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000416

ClinVar

ClinVar submissions

Significance: Likely 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	-0.64
CADD	Benign	4.2
DANN	Benign	0.72
PhyloP100		-0.095

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: rs759894262; hg19: chr4-183267973;