rs3762096

Positions:

• chr10-96376493-G-A
• chr10-96376493-G-T

Variant summary

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

The NM_012465.4(TLL2):​c.2448+199C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 152,198 control chromosomes in the GnomAD database, including 8,975 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 0.32 (8975 hom., cov: 33)
• Consequence: TLL2 NM_012465.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0550

Genes affected

TLL2 (HGNC:11844): (tolloid like 2) This gene encodes an astacin-like zinc-dependent metalloprotease and is a subfamily member of the metzincin family. Unlike other family members, a similar protein in mice does not cleave procollagen C-propeptides or chordin. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLL2	NM_012465.4	c.2448+199C>T		intron_variant		ENST00000357947.4	NP_036597.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLL2	ENST00000357947.4	c.2448+199C>T		intron_variant		1	NM_012465.4	ENSP00000350630.3

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49450 AN: 152080 Hom.: 8972 Cov.: 33

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.644

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.365

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

GnomAD4 genome AF: 0.325 AC: 49454 AN: 152198 Hom.: 8975 Cov.: 33 AF XY: 0.330 AC XY: 24566 AN XY: 74406

Gnomad4 AFR AF: 0.183

Gnomad4 AMR AF: 0.415

Gnomad4 ASJ AF: 0.448

Gnomad4 EAS AF: 0.644

Gnomad4 SAS AF: 0.428

Gnomad4 FIN AF: 0.356

Gnomad4 NFE AF: 0.348

Gnomad4 OTH AF: 0.367

Alfa AF: 0.351 Hom.: 19640

Bravo AF: 0.325

Asia WGS AF: 0.525 AC: 1825 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.32
DANN	Benign	0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs3762096; hg19: chr10-98136250;