chr6-81749628-CT-C

Variant names:

• chr6-81749628-CT-C
• rs545732284
• NM_017633.3:c.*66delA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_017633.3(TENT5A):​c.*66delA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 1,008,774 control chromosomes in the GnomAD database, including 592 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.066 (437 hom., cov: 30)
  • Exomes 𝑓: 0.19 (155 hom.)
• Consequence: TENT5A NM_017633.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.316
• Publications: 0 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 -10 ACMG points.

• BP6: Variant 6-81749628-CT-C is Benign according to our data. Variant chr6-81749628-CT-C is described in ClinVar as Benign. ClinVar VariationId is 1282756.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017633.3. 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
	TENT5A	NM_017633.3	MANE Select	c.*66delA		3_prime_UTR	Exon 3 of 3	NP_060103.2	Q96IP4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TENT5A	ENST00000320172.11	TSL:1 MANE Select	c.*66delA		3_prime_UTR	Exon 3 of 3	ENSP00000318298.6	Q96IP4-1
	TENT5A	ENST00000369756.3	TSL:1	c.*66delA		3_prime_UTR	Exon 3 of 3	ENSP00000358771.3	Q5TF85
	TENT5A	ENST00000369754.7	TSL:1	c.*66delA		3_prime_UTR	Exon 3 of 3	ENSP00000358769.3	Q96IP4-2

Frequencies

GnomAD3 genomes AF: 0.0660 AC: 9209 AN: 139590 Hom.: 439 Cov.: 30

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.0229

Gnomad AMR AF: 0.0356

Gnomad ASJ AF: 0.0312

Gnomad EAS AF: 0.0170

Gnomad SAS AF: 0.0658

Gnomad FIN AF: 0.0158

Gnomad MID AF: 0.0582

Gnomad NFE AF: 0.0427

Gnomad OTH AF: 0.0608

GnomAD4 exome AF: 0.191 AC: 165862 AN: 869206 Hom.: 155 Cov.: 0 AF XY: 0.190 AC XY: 80983 AN XY: 425324

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.268 AC: 5574 AN: 20762

American (AMR) AF: 0.184 AC: 3248 AN: 17658

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 2555 AN: 12668

East Asian (EAS) AF: 0.198 AC: 4736 AN: 23954

South Asian (SAS) AF: 0.189 AC: 8364 AN: 44242

European-Finnish (FIN) AF: 0.176 AC: 4721 AN: 26900

Middle Eastern (MID) AF: 0.174 AC: 593 AN: 3416

European-Non Finnish (NFE) AF: 0.188 AC: 128622 AN: 683624

Other (OTH) AF: 0.207 AC: 7449 AN: 35982

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0660 AC: 9211 AN: 139568 Hom.: 437 Cov.: 30 AF XY: 0.0631 AC XY: 4260 AN XY: 67504

African (AFR) AF: 0.138 AC: 5235 AN: 38034

American (AMR) AF: 0.0355 AC: 498 AN: 14014

Ashkenazi Jewish (ASJ) AF: 0.0312 AC: 103 AN: 3298

East Asian (EAS) AF: 0.0169 AC: 81 AN: 4796

South Asian (SAS) AF: 0.0661 AC: 287 AN: 4344

European-Finnish (FIN) AF: 0.0158 AC: 130 AN: 8236

Middle Eastern (MID) AF: 0.0526 AC: 14 AN: 266

European-Non Finnish (NFE) AF: 0.0428 AC: 2728 AN: 63812

Other (OTH) AF: 0.0607 AC: 115 AN: 1896

Alfa AF: 0.00471 Hom.: 2

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.32
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: rs545732284; hg19: chr6-82459345;