NM_001080477.4:c.3579T>C

Variant names:

• chr4-182743369-T-C
• rs7654255
• NM_001080477.4:c.3579T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001080477.4(TENM3):​c.3579T>C​(p.Tyr1193Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 1,613,556 control chromosomes in the GnomAD database, including 69,117 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (6832 hom., cov: 33)
  • Exomes 𝑓: 0.29 (62285 hom.)
• Consequence: TENM3 NM_001080477.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.552
• Publications: 15 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 4-182743369-T-C is Benign according to our data. Variant chr4-182743369-T-C is described in ClinVar as Benign. ClinVar VariationId is 257350.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.552 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.342 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.3579T>C	p.Tyr1193Tyr	synonymous	Exon 19 of 28	NP_001073946.1	Q9P273
	TENM3	NM_001415969.1		c.3579T>C	p.Tyr1193Tyr	synonymous	Exon 19 of 29	NP_001402898.1
	TENM3	NM_001415970.1		c.3579T>C	p.Tyr1193Tyr	synonymous	Exon 19 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.3579T>C	p.Tyr1193Tyr	synonymous	Exon 19 of 28	ENSP00000424226.1	Q9P273
	TENM3	ENST00000851056.1		c.3627T>C	p.Tyr1209Tyr	synonymous	Exon 21 of 31	ENSP00000521125.1
	TENM3	ENST00000851057.1		c.3624T>C	p.Tyr1208Tyr	synonymous	Exon 21 of 31	ENSP00000521126.1

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44557 AN: 151996 Hom.: 6830 Cov.: 33

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.282

GnomAD2 exomes AF: 0.257 AC: 63948 AN: 249150 AF XY: 0.254

Gnomad AFR exome AF: 0.346

Gnomad AMR exome AF: 0.135

Gnomad ASJ exome AF: 0.260

Gnomad EAS exome AF: 0.153

Gnomad FIN exome AF: 0.329

Gnomad NFE exome AF: 0.304

Gnomad OTH exome AF: 0.263

GnomAD4 exome AF: 0.286 AC: 418634 AN: 1461442 Hom.: 62285 Cov.: 35 AF XY: 0.283 AC XY: 205808 AN XY: 727016

African (AFR) AF: 0.344 AC: 11506 AN: 33476

American (AMR) AF: 0.142 AC: 6342 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 6715 AN: 26136

East Asian (EAS) AF: 0.144 AC: 5710 AN: 39698

South Asian (SAS) AF: 0.180 AC: 15562 AN: 86250

European-Finnish (FIN) AF: 0.326 AC: 17432 AN: 53398

Middle Eastern (MID) AF: 0.208 AC: 1198 AN: 5766

European-Non Finnish (NFE) AF: 0.304 AC: 337535 AN: 1111638

Other (OTH) AF: 0.276 AC: 16634 AN: 60366

GnomAD4 genome AF: 0.293 AC: 44587 AN: 152114 Hom.: 6832 Cov.: 33 AF XY: 0.288 AC XY: 21415 AN XY: 74364

African (AFR) AF: 0.347 AC: 14394 AN: 41498

American (AMR) AF: 0.184 AC: 2819 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 937 AN: 3464

East Asian (EAS) AF: 0.153 AC: 790 AN: 5158

South Asian (SAS) AF: 0.173 AC: 833 AN: 4824

European-Finnish (FIN) AF: 0.322 AC: 3407 AN: 10576

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.304 AC: 20639 AN: 67986

Other (OTH) AF: 0.282 AC: 596 AN: 2110

Alfa AF: 0.296 Hom.: 20633

Bravo AF: 0.288

Asia WGS AF: 0.205 AC: 714 AN: 3478

EpiCase AF: 0.286

EpiControl AF: 0.286

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.46
DANN	Benign	0.23
PhyloP100		-0.55
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: rs7654255; hg19: chr4-183664522; COSMIC: COSV69308556;