16-88809365-TCTG-T

Variant names:

• chr16-88809365-TCTG-T
• rs8191500
• NM_000485.3:c.*330_*332delCAG

Variant summary

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

The NM_000485.3(APRT):​c.*330_*332delCAG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00679 in 486,742 control chromosomes in the GnomAD database, including 90 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.017 (76 hom., cov: 34)
  • Exomes 𝑓: 0.0022 (14 hom.)
• Consequence: APRT NM_000485.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.155
• Publications: 0 publications found

Genes affected

APRT (HGNC:626): (adenine phosphoribosyltransferase) Adenine phosphoribosyltransferase belongs to the purine/pyrimidine phosphoribosyltransferase family. A conserved feature of this gene is the distribution of CpG dinucleotides. This enzyme catalyzes the formation of AMP and inorganic pyrophosphate from adenine and 5-phosphoribosyl-1-pyrophosphate (PRPP). It also produces adenine as a by-product of the polyamine biosynthesis pathway. A homozygous deficiency in this enzyme causes 2,8-dihydroxyadenine urolithiasis. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

CDT1 (HGNC:24576): (chromatin licensing and DNA replication factor 1) The protein encoded by this gene is involved in the formation of the pre-replication complex that is necessary for DNA replication. The encoded protein can bind geminin, which prevents replication and may function to prevent this protein from initiating replication at inappropriate origins. Phosphorylation of this protein by cyclin A-dependent kinases results in degradation of the protein. [provided by RefSeq, Mar 2011]

CDT1 Gene-Disease associations (from GenCC):

• Meier-Gorlin syndrome 4

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen
• Meier-Gorlin syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 16-88809365-TCTG-T is Benign according to our data. Variant chr16-88809365-TCTG-T is described in ClinVar as Benign. ClinVar VariationId is 1234021.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0574 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000485.3. 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
	APRT	NM_000485.3	MANE Select	c.*330_*332delCAG		3_prime_UTR	Exon 5 of 5	NP_000476.1	P07741-1
	CDT1	NM_030928.4	MANE Select	c.*1088_*1090delCTG		downstream_gene	N/A	NP_112190.2	Q9H211
	APRT	NM_001030018.2		c.*334_*336delCAG		downstream_gene	N/A	NP_001025189.1	P07741-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APRT	ENST00000378364.8	TSL:1 MANE Select	c.*330_*332delCAG		3_prime_UTR	Exon 5 of 5	ENSP00000367615.3	P07741-1
	CDT1	ENST00000301019.9	TSL:1 MANE Select	c.*1088_*1090delCTG		downstream_gene	N/A	ENSP00000301019.4	Q9H211
	APRT	ENST00000912471.1		c.*330_*332delCAG		downstream_gene	N/A	ENSP00000582530.1

Frequencies

GnomAD3 genomes AF: 0.0169 AC: 2566 AN: 152250 Hom.: 76 Cov.: 34

Gnomad AFR AF: 0.0595

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.0100

GnomAD2 exomes AF: 0.00374 AC: 448 AN: 119936 AF XY: 0.00303

Gnomad AFR exome AF: 0.0611

Gnomad AMR exome AF: 0.00304

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000459

Gnomad OTH exome AF: 0.000792

GnomAD4 exome AF: 0.00221 AC: 738 AN: 334374 Hom.: 14 AF XY: 0.00167 AC XY: 313 AN XY: 187546

African (AFR) AF: 0.0566 AC: 574 AN: 10140

American (AMR) AF: 0.00328 AC: 91 AN: 27748

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11508

East Asian (EAS) AF: 0.00 AC: 0 AN: 12256

South Asian (SAS) AF: 0.0000684 AC: 4 AN: 58438

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 14010

Middle Eastern (MID) AF: 0.000340 AC: 1 AN: 2942

European-Non Finnish (NFE) AF: 0.0000387 AC: 7 AN: 180664

Other (OTH) AF: 0.00366 AC: 61 AN: 16668

GnomAD4 genome AF: 0.0169 AC: 2568 AN: 152368 Hom.: 76 Cov.: 34 AF XY: 0.0161 AC XY: 1198 AN XY: 74514

African (AFR) AF: 0.0594 AC: 2468 AN: 41580

American (AMR) AF: 0.00457 AC: 70 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68044

Other (OTH) AF: 0.00992 AC: 21 AN: 2116

Alfa AF: 0.00877 Hom.: 5

Bravo AF: 0.0191

Asia WGS AF: 0.00289 AC: 10 AN: 3478

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		0.15
Mutation Taster		=100/0	polymorphism

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: rs8191500; hg19: chr16-88875773;