NM_012465.4:c.175+13062A>G

Variant names:

• chr10-96500449-T-C
• rs11188799
• NM_012465.4:c.175+13062A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012465.4(TLL2):​c.175+13062A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 152,136 control chromosomes in the GnomAD database, including 6,393 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 0.29 (6393 hom., cov: 32)
• Consequence: TLL2 NM_012465.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.197
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.495 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.175+13062A>G		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.175+13062A>G		intron	N/A	ENSP00000350630.3
	TLL2	ENST00000469598.1	TSL:2	n.408+13062A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43361 AN: 152018 Hom.: 6388 Cov.: 32

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.512

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.175

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.289

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

GnomAD4 genome AF: 0.285 AC: 43397 AN: 152136 Hom.: 6393 Cov.: 32 AF XY: 0.285 AC XY: 21238 AN XY: 74392

African (AFR) AF: 0.255 AC: 10601 AN: 41492

American (AMR) AF: 0.304 AC: 4651 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1040 AN: 3468

East Asian (EAS) AF: 0.512 AC: 2643 AN: 5166

South Asian (SAS) AF: 0.305 AC: 1471 AN: 4824

European-Finnish (FIN) AF: 0.252 AC: 2666 AN: 10594

Middle Eastern (MID) AF: 0.188 AC: 55 AN: 292

European-Non Finnish (NFE) AF: 0.283 AC: 19241 AN: 67986

Other (OTH) AF: 0.291 AC: 614 AN: 2110

Alfa AF: 0.285 Hom.: 18349

Bravo AF: 0.291

Asia WGS AF: 0.387 AC: 1347 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.2
DANN	Benign	0.39
PhyloP100		-0.20
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: rs11188799; hg19: chr10-98260206;