4-181486725-T-C

Position:

• chr4-181486725-T-C

Variant summary

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

The XM_017008385.2(TENM3):​c.-400+38953T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 151,954 control chromosomes in the GnomAD database, including 20,989 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 0.52 (20989 hom., cov: 32)
• Consequence: TENM3 XM_017008385.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0190

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TENM3	XM_017008385.2	c.-400+38953T>C		intron_variant			XP_016863874.1
TENM3	XM_017008389.2	c.-400+38953T>C		intron_variant			XP_016863878.1
TENM3	XM_017008390.2	c.-400+38953T>C		intron_variant			XP_016863879.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78648 AN: 151838 Hom.: 20986 Cov.: 32

Gnomad AFR AF: 0.408

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.564

Gnomad EAS AF: 0.377

Gnomad SAS AF: 0.529

Gnomad FIN AF: 0.522

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.592

Gnomad OTH AF: 0.545

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

GnomAD4 genome AF: 0.518 AC: 78668 AN: 151954 Hom.: 20989 Cov.: 32 AF XY: 0.515 AC XY: 38250 AN XY: 74252

Gnomad4 AFR AF: 0.408

Gnomad4 AMR AF: 0.510

Gnomad4 ASJ AF: 0.564

Gnomad4 EAS AF: 0.376

Gnomad4 SAS AF: 0.529

Gnomad4 FIN AF: 0.522

Gnomad4 NFE AF: 0.592

Gnomad4 OTH AF: 0.542

Alfa AF: 0.564 Hom.: 6084

Bravo AF: 0.511

Asia WGS AF: 0.437 AC: 1518 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	14
DANN	Benign	0.40

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17198973; hg19: chr4-182407878;