chr10-96413689-C-G

Variant names:

• chr10-96413689-C-G
• rs1923694
• NM_012465.4:c.924-373G>C

Variant summary

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

The NM_012465.4(TLL2):​c.924-373G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,096 control chromosomes in the GnomAD database, including 1,044 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 0.11 (1044 hom., cov: 32)
• Consequence: TLL2 NM_012465.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.642
• Publications: 0 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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLL2	NM_012465.4	c.924-373G>C		intron_variant	Intron 7 of 20	ENST00000357947.4	NP_036597.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLL2	ENST00000357947.4	c.924-373G>C		intron_variant	Intron 7 of 20	1	NM_012465.4	ENSP00000350630.3
TLL2	ENST00000469598.1	n.1001-373G>C		intron_variant	Intron 6 of 12	2

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16653 AN: 151978 Hom.: 1043 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.0685

Gnomad ASJ AF: 0.0885

Gnomad EAS AF: 0.0349

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.0826

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.0954

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

GnomAD4 genome AF: 0.110 AC: 16666 AN: 152096 Hom.: 1044 Cov.: 32 AF XY: 0.108 AC XY: 8055 AN XY: 74346

African (AFR) AF: 0.141 AC: 5829 AN: 41480

American (AMR) AF: 0.0684 AC: 1046 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0885 AC: 307 AN: 3470

East Asian (EAS) AF: 0.0350 AC: 181 AN: 5172

South Asian (SAS) AF: 0.160 AC: 770 AN: 4808

European-Finnish (FIN) AF: 0.0826 AC: 875 AN: 10596

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.108 AC: 7308 AN: 67980

Other (OTH) AF: 0.0972 AC: 205 AN: 2108

Alfa AF: 0.111 Hom.: 107

Bravo AF: 0.108

Asia WGS AF: 0.0960 AC: 334 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.3
DANN	Benign	0.58
PhyloP100		0.64
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: rs1923694; hg19: chr10-98173446;