6-81515245-A-G

Variant names:

• chr6-81515245-A-G
• rs9449341
• ENST00000412306.1:c.223-20132T>C

Variant summary

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

The ENST00000412306.1(TENT5A):​c.223-20132T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 150,846 control chromosomes in the GnomAD database, including 3,874 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 0.21 (3874 hom., cov: 30)
• Consequence: TENT5A ENST00000412306.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 6 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

LOC105377871 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000412306.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TENT5A	ENST00000412306.1	TSL:3	c.223-20132T>C		intron	N/A	ENSP00000401884.1	H0Y5Y3

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32137 AN: 150730 Hom.: 3874 Cov.: 30

Gnomad AFR AF: 0.0989

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.217

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.244

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

GnomAD4 genome AF: 0.213 AC: 32143 AN: 150846 Hom.: 3874 Cov.: 30 AF XY: 0.215 AC XY: 15792 AN XY: 73586

African (AFR) AF: 0.0989 AC: 4064 AN: 41094

American (AMR) AF: 0.261 AC: 3949 AN: 15126

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 947 AN: 3464

East Asian (EAS) AF: 0.295 AC: 1500 AN: 5088

South Asian (SAS) AF: 0.222 AC: 1061 AN: 4776

European-Finnish (FIN) AF: 0.299 AC: 3077 AN: 10304

Middle Eastern (MID) AF: 0.209 AC: 61 AN: 292

European-Non Finnish (NFE) AF: 0.247 AC: 16750 AN: 67720

Other (OTH) AF: 0.243 AC: 504 AN: 2076

Alfa AF: 0.245 Hom.: 3787

Bravo AF: 0.206

Asia WGS AF: 0.234 AC: 811 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.081
DANN	Benign	0.14
PhyloP100		-1.1

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs9449341;

hg19: chr6-82224962;