chr10-96394513-G-A

Variant names:

• chr10-96394513-G-A
• rs1923696
• NM_012465.4:c.1726+674C>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.1726+674C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 152,080 control chromosomes in the GnomAD database, including 7,381 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 0.30 (7381 hom., cov: 32)
• Consequence: TLL2 NM_012465.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.618
• Publications: 1 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012465.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLL2	NM_012465.4	MANE Select	c.1726+674C>T		intron	N/A	NP_036597.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLL2	ENST00000357947.4	TSL:1 MANE Select	c.1726+674C>T		intron	N/A	ENSP00000350630.3

Frequencies

GnomAD3 genomes AF: 0.303 AC: 46082 AN: 151962 Hom.: 7383 Cov.: 32

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.377

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.318

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

GnomAD4 genome AF: 0.303 AC: 46090 AN: 152080 Hom.: 7381 Cov.: 32 AF XY: 0.299 AC XY: 22223 AN XY: 74354

African (AFR) AF: 0.214 AC: 8890 AN: 41468

American (AMR) AF: 0.309 AC: 4722 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.377 AC: 1306 AN: 3464

East Asian (EAS) AF: 0.152 AC: 787 AN: 5168

South Asian (SAS) AF: 0.195 AC: 940 AN: 4824

European-Finnish (FIN) AF: 0.346 AC: 3657 AN: 10566

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.363 AC: 24709 AN: 67980

Other (OTH) AF: 0.315 AC: 666 AN: 2114

Alfa AF: 0.340 Hom.: 1102

Bravo AF: 0.300

Asia WGS AF: 0.178 AC: 621 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	13
DANN	Benign	0.90
PhyloP100		0.62
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1923696; hg19: chr10-98154270;