chr10-96376493-G-A

Variant names:

• chr10-96376493-G-A
• rs3762096
• NM_012465.4:c.2448+199C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

ENSG00000310117 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TLL2	NM_012465.4	c.2448+199C>T		intron_variant	Intron 18 of 20	ENST00000357947.4	NP_036597.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLL2	ENST00000357947.4	c.2448+199C>T		intron_variant	Intron 18 of 20	1	NM_012465.4	ENSP00000350630.3
ENSG00000310117	ENST00000847278.1	n.80-65G>A		intron_variant	Intron 1 of 1

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

African (AFR) AF: 0.183 AC: 7615 AN: 41526

American (AMR) AF: 0.415 AC: 6346 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 1556 AN: 3472

East Asian (EAS) AF: 0.644 AC: 3334 AN: 5176

South Asian (SAS) AF: 0.428 AC: 2067 AN: 4826

European-Finnish (FIN) AF: 0.356 AC: 3767 AN: 10590

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.348 AC: 23638 AN: 67996

Other (OTH) AF: 0.367 AC: 775 AN: 2114

Alfa AF: 0.345 Hom.: 40411

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
PhyloP100		-0.055
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: rs3762096; hg19: chr10-98136250;