chr6-81594518-T-C

Variant names:

• chr6-81594518-T-C
• rs13437553
• ENST00000412306.1:c.223-99405A>G

Variant summary

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

The ENST00000412306.1(TENT5A):​c.223-99405A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 152,028 control chromosomes in the GnomAD database, including 3,872 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 0.22 (3872 hom., cov: 31)
• Consequence: TENT5A ENST00000412306.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.446
• Publications: 5 publications found

Genes affected

TENT5A (HGNC:18345): (terminal nucleotidyltransferase 5A) Enables RNA binding activity. Predicted to be involved in mRNA stabilization. Predicted to act upstream of or within response to bacterium. Implicated in lung non-small cell carcinoma; osteoarthritis; and osteogenesis imperfecta type 18. [provided by Alliance of Genome Resources, Apr 2022]

TENT5A Gene-Disease associations (from GenCC):

• osteogenesis imperfecta, type 18

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• osteogenesis imperfecta

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TENT5A	ENST00000412306.1	c.223-99405A>G		intron_variant	Intron 1 of 2	3		ENSP00000401884.1

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33510 AN: 151910 Hom.: 3868 Cov.: 31

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.217

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.233

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

GnomAD4 genome AF: 0.221 AC: 33534 AN: 152028 Hom.: 3872 Cov.: 31 AF XY: 0.222 AC XY: 16510 AN XY: 74284

African (AFR) AF: 0.186 AC: 7710 AN: 41464

American (AMR) AF: 0.256 AC: 3916 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 900 AN: 3472

East Asian (EAS) AF: 0.192 AC: 985 AN: 5128

South Asian (SAS) AF: 0.179 AC: 864 AN: 4828

European-Finnish (FIN) AF: 0.296 AC: 3126 AN: 10556

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.225 AC: 15290 AN: 67998

Other (OTH) AF: 0.231 AC: 488 AN: 2108

Alfa AF: 0.218 Hom.: 4230

Bravo AF: 0.219

Asia WGS AF: 0.185 AC: 642 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.3
DANN	Benign	0.38
PhyloP100		0.45

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs13437553; hg19: chr6-82304235;