rs13340295

Variant names:

• chr4-182728947-G-A
• rs13340295
• NM_001080477.4:c.2369-18G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-182728947-G-A
• chr4-182728947-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001080477.4(TENM3):​c.2369-18G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0584 in 1,605,396 control chromosomes in the GnomAD database, including 3,474 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.081 (779 hom., cov: 32)
  • Exomes 𝑓: 0.056 (2695 hom.)
• Consequence: TENM3 NM_001080477.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.00600
• Publications: 1 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: G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics
• microphthalmia, isolated, with coloboma

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 4-182728947-G-A is Benign according to our data. Variant chr4-182728947-G-A is described in ClinVar as Benign. ClinVar VariationId is 257348.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.165 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.2369-18G>A		intron	N/A	NP_001073946.1	Q9P273
	TENM3	NM_001415969.1		c.2369-18G>A		intron	N/A	NP_001402898.1
	TENM3	NM_001415970.1		c.2369-18G>A		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.2369-18G>A		intron	N/A	ENSP00000424226.1	Q9P273
	TENM3	ENST00000851056.1		c.2417-18G>A		intron	N/A	ENSP00000521125.1
	TENM3	ENST00000851057.1		c.2414-18G>A		intron	N/A	ENSP00000521126.1

Frequencies

GnomAD3 genomes AF: 0.0813 AC: 12347 AN: 151794 Hom.: 774 Cov.: 32

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.0565

Gnomad ASJ AF: 0.0444

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.0418

Gnomad FIN AF: 0.0140

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0562

Gnomad OTH AF: 0.0755

GnomAD2 exomes AF: 0.0523 AC: 12883 AN: 246326 AF XY: 0.0515

Gnomad AFR exome AF: 0.174

Gnomad AMR exome AF: 0.0380

Gnomad ASJ exome AF: 0.0452

Gnomad EAS exome AF: 0.0000560

Gnomad FIN exome AF: 0.0159

Gnomad NFE exome AF: 0.0577

Gnomad OTH exome AF: 0.0573

GnomAD4 exome AF: 0.0560 AC: 81338 AN: 1453492 Hom.: 2695 Cov.: 30 AF XY: 0.0553 AC XY: 39975 AN XY: 723070

African (AFR) AF: 0.169 AC: 5642 AN: 33312

American (AMR) AF: 0.0398 AC: 1773 AN: 44510

Ashkenazi Jewish (ASJ) AF: 0.0447 AC: 1164 AN: 26018

East Asian (EAS) AF: 0.000152 AC: 6 AN: 39594

South Asian (SAS) AF: 0.0469 AC: 4018 AN: 85678

European-Finnish (FIN) AF: 0.0173 AC: 921 AN: 53368

Middle Eastern (MID) AF: 0.0955 AC: 549 AN: 5750

European-Non Finnish (NFE) AF: 0.0575 AC: 63516 AN: 1105192

Other (OTH) AF: 0.0624 AC: 3749 AN: 60070

GnomAD4 genome AF: 0.0814 AC: 12361 AN: 151904 Hom.: 779 Cov.: 32 AF XY: 0.0789 AC XY: 5856 AN XY: 74264

African (AFR) AF: 0.168 AC: 6973 AN: 41386

American (AMR) AF: 0.0564 AC: 860 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.0444 AC: 154 AN: 3468

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5172

South Asian (SAS) AF: 0.0410 AC: 197 AN: 4808

European-Finnish (FIN) AF: 0.0140 AC: 147 AN: 10536

Middle Eastern (MID) AF: 0.154 AC: 45 AN: 292

European-Non Finnish (NFE) AF: 0.0562 AC: 3821 AN: 67972

Other (OTH) AF: 0.0747 AC: 158 AN: 2114

Alfa AF: 0.0695 Hom.: 578

Bravo AF: 0.0890

Asia WGS AF: 0.0340 AC: 118 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.87
CADD	Benign	0.66
DANN	Benign	0.26
PhyloP100		-0.0060
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: rs13340295; hg19: chr4-183650100;