NM_012464.5:c.170-10726C>T

Variant names:

• chr4-165978655-C-T
• rs10031332
• NM_012464.5:c.170-10726C>T

Variant summary

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

The NM_012464.5(TLL1):​c.170-10726C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0868 in 152,180 control chromosomes in the GnomAD database, including 1,779 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 0.087 (1779 hom., cov: 33)
• Consequence: TLL1 NM_012464.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.68

Genes affected

TLL1 (HGNC:11843): (tolloid like 1) This gene encodes an astacin-like, zinc-dependent, metalloprotease that belongs to the peptidase M12A family. This protease processes procollagen C-propeptides, such as chordin, pro-biglycan and pro-lysyl oxidase. Studies in mice suggest that this gene plays multiple roles in the development of mammalian heart, and is essential for the formation of the interventricular septum. Allelic variants of this gene are associated with atrial septal defect type 6. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLL1	NM_012464.5	c.170-10726C>T		intron_variant	Intron 1 of 20	ENST00000061240.7	NP_036596.3
TLL1	NM_001204760.2	c.170-10726C>T		intron_variant	Intron 1 of 9		NP_001191689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLL1	ENST00000061240.7	c.170-10726C>T		intron_variant	Intron 1 of 20	1	NM_012464.5	ENSP00000061240.2

Frequencies

GnomAD3 genomes AF: 0.0865 AC: 13149 AN: 152062 Hom.: 1768 Cov.: 33

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0375

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.0421

Gnomad SAS AF: 0.0259

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00169

Gnomad OTH AF: 0.0684

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

GnomAD4 genome AF: 0.0868 AC: 13202 AN: 152180 Hom.: 1779 Cov.: 33 AF XY: 0.0836 AC XY: 6221 AN XY: 74418

Gnomad4 AFR AF: 0.289

Gnomad4 AMR AF: 0.0375

Gnomad4 ASJ AF: 0.00778

Gnomad4 EAS AF: 0.0422

Gnomad4 SAS AF: 0.0253

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00169

Gnomad4 OTH AF: 0.0710

Alfa AF: 0.0123 Hom.: 326

Bravo AF: 0.0970

Asia WGS AF: 0.0380 AC: 130 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.3
DANN	Benign	0.57

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: rs10031332; hg19: chr4-166899807;