chr4-182216245-T-C

Position:

• chr4-182216245-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001415969.1(TENM3):​c.-76+72084T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 152,070 control chromosomes in the GnomAD database, including 25,262 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.57 (25262 hom., cov: 33)
• Consequence: TENM3 NM_001415969.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.224

Genes affected

TENM3 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TENM3	NM_001415969.1	c.-76+72084T>C		intron_variant			NP_001402898.1
TENM3	NM_001415970.1	c.-76+71491T>C		intron_variant			NP_001402899.1
TENM3	NM_001415968.1	c.-76+71491T>C		intron_variant			NP_001402897.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TENM3	ENST00000513201.1	n.175+72084T>C		intron_variant		1
TENM3	ENST00000512480.5	c.-76+71491T>C		intron_variant		3		ENSP00000421320.1

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86636 AN: 151952 Hom.: 25255 Cov.: 33

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.530

Gnomad AMR AF: 0.618

Gnomad ASJ AF: 0.605

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.562

Gnomad FIN AF: 0.604

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.639

Gnomad OTH AF: 0.606

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.570 AC: 86677 AN: 152070 Hom.: 25262 Cov.: 33 AF XY: 0.567 AC XY: 42191 AN XY: 74356

Gnomad4 AFR AF: 0.452

Gnomad4 AMR AF: 0.618

Gnomad4 ASJ AF: 0.605

Gnomad4 EAS AF: 0.381

Gnomad4 SAS AF: 0.562

Gnomad4 FIN AF: 0.604

Gnomad4 NFE AF: 0.638

Gnomad4 OTH AF: 0.600

Alfa AF: 0.629 Hom.: 60511

Bravo AF: 0.564

Asia WGS AF: 0.460 AC: 1602 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.4
DANN	Benign	0.59

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2726807; hg19: chr4-183137398;