rs11223

Variant names:

• chr4-182799697-C-T
• rs11223
• NM_001080477.4:c.7446C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-182799697-C-T
• chr4-182799697-C-G

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001080477.4(TENM3):​c.7446C>T​(p.Gly2482Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 1,549,364 control chromosomes in the GnomAD database, including 13,281 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2934 hom., cov: 33)
  • Exomes 𝑓: 0.11 (10347 hom.)
• Consequence: TENM3 NM_001080477.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.125
• Publications: 11 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BP6: Variant 4-182799697-C-T is Benign according to our data. Variant chr4-182799697-C-T is described in ClinVar as Benign. ClinVar VariationId is 257355.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.125 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.32 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.7446C>T	p.Gly2482Gly	synonymous	Exon 28 of 28	NP_001073946.1	Q9P273
	TENM3	NM_001415969.1		c.7467C>T	p.Gly2489Gly	synonymous	Exon 29 of 29	NP_001402898.1
	TENM3	NM_001415970.1		c.7467C>T	p.Gly2489Gly	synonymous	Exon 29 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.7446C>T	p.Gly2482Gly	synonymous	Exon 28 of 28	ENSP00000424226.1	Q9P273
	TENM3	ENST00000851056.1		c.7515C>T	p.Gly2505Gly	synonymous	Exon 31 of 31	ENSP00000521125.1
	TENM3	ENST00000851057.1		c.7512C>T	p.Gly2504Gly	synonymous	Exon 31 of 31	ENSP00000521126.1

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25608 AN: 152090 Hom.: 2913 Cov.: 33

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.0521

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.146

GnomAD2 exomes AF: 0.131 AC: 19526 AN: 149450 AF XY: 0.128

Gnomad AFR exome AF: 0.329

Gnomad AMR exome AF: 0.151

Gnomad ASJ exome AF: 0.119

Gnomad EAS exome AF: 0.247

Gnomad FIN exome AF: 0.0531

Gnomad NFE exome AF: 0.104

Gnomad OTH exome AF: 0.115

GnomAD4 exome AF: 0.113 AC: 157589 AN: 1397156 Hom.: 10347 Cov.: 33 AF XY: 0.112 AC XY: 77132 AN XY: 689194

African (AFR) AF: 0.343 AC: 10819 AN: 31540

American (AMR) AF: 0.147 AC: 5231 AN: 35478

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 3027 AN: 25114

East Asian (EAS) AF: 0.179 AC: 6394 AN: 35704

South Asian (SAS) AF: 0.124 AC: 9783 AN: 79164

European-Finnish (FIN) AF: 0.0545 AC: 2613 AN: 47958

Middle Eastern (MID) AF: 0.140 AC: 799 AN: 5692

European-Non Finnish (NFE) AF: 0.104 AC: 111718 AN: 1078564

Other (OTH) AF: 0.124 AC: 7205 AN: 57942

GnomAD4 genome AF: 0.169 AC: 25672 AN: 152208 Hom.: 2934 Cov.: 33 AF XY: 0.166 AC XY: 12319 AN XY: 74406

African (AFR) AF: 0.324 AC: 13468 AN: 41526

American (AMR) AF: 0.136 AC: 2076 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 417 AN: 3472

East Asian (EAS) AF: 0.237 AC: 1218 AN: 5140

South Asian (SAS) AF: 0.123 AC: 595 AN: 4826

European-Finnish (FIN) AF: 0.0521 AC: 553 AN: 10616

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.102 AC: 6903 AN: 68000

Other (OTH) AF: 0.146 AC: 309 AN: 2114

Alfa AF: 0.122 Hom.: 828

Bravo AF: 0.185

Asia WGS AF: 0.169 AC: 588 AN: 3478

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	-0.30
CADD	Benign	12
DANN	Benign	0.83
PhyloP100		0.13
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: rs11223; hg19: chr4-183720850; COSMIC: COSV69308415;