7-33014505-T-TAAG

Variant names:

• chr7-33014505-T-TAAG
• rs199721569
• NM_001002010.5:c.*224_*225insCTT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS1

The NM_001002010.5(NT5C3A):​c.*224_*225insCTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00040 (0 hom., cov: 0)
  • Exomes 𝑓: 0.010 (3 hom.)
  • Failed GnomAD Quality Control
• Consequence: NT5C3A NM_001002010.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.699
• Publications: 2 publications found

Genes affected

NT5C3A (HGNC:17820): (5'-nucleotidase, cytosolic IIIA) This gene encodes a member of the 5'-nucleotidase family of enzymes that catalyze the dephosphorylation of nucleoside 5'-monophosphates. The encoded protein is the type 1 isozyme of pyrimidine 5' nucleotidase and catalyzes the dephosphorylation of pyrimidine 5' monophosphates. Mutations in this gene are a cause of hemolytic anemia due to uridine 5-prime monophosphate hydrolase deficiency. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and pseudogenes of this gene are located on the long arm of chromosomes 3 and 4. [provided by RefSeq, Mar 2012]

NT5C3A Gene-Disease associations (from GenCC):

• hemolytic anemia due to pyrimidine 5' nucleotidase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000401 (58/144494) while in subpopulation AFR AF = 0.001 (40/39856). AF 95% confidence interval is 0.000757. There are 0 homozygotes in GnomAd4. There are 30 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001002010.5. 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
	NT5C3A	NM_001002010.5	MANE Select	c.*224_*225insCTT		3_prime_UTR	Exon 9 of 9	NP_001002010.2	X6RM59
	NT5C3A	NM_001374335.1		c.*224_*225insCTT		3_prime_UTR	Exon 8 of 8	NP_001361264.1
	NT5C3A	NM_001002009.3		c.*224_*225insCTT		3_prime_UTR	Exon 10 of 10	NP_001002009.1	Q9H0P0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NT5C3A	ENST00000610140.7	TSL:1 MANE Select	c.*224_*225insCTT		3_prime_UTR	Exon 9 of 9	ENSP00000476480.2	X6RM59
	NT5C3A	ENST00000456458.5	TSL:1	n.*1125_*1126insCTT		non_coding_transcript_exon	Exon 10 of 10	ENSP00000389676.2	F8WDR0
	NT5C3A	ENST00000456458.5	TSL:1	n.*1125_*1126insCTT		3_prime_UTR	Exon 10 of 10	ENSP00000389676.2	F8WDR0

Frequencies

GnomAD3 genomes AF: 0.000388 AC: 56 AN: 144386 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000956

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000342

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000397

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000124

Gnomad OTH AF: 0.000504

GnomAD2 exomes AF: 0.0123 AC: 1030 AN: 83480 AF XY: 0.0116

Gnomad AFR exome AF: 0.00489

Gnomad AMR exome AF: 0.0217

Gnomad ASJ exome AF: 0.0102

Gnomad EAS exome AF: 0.00372

Gnomad FIN exome AF: 0.0298

Gnomad NFE exome AF: 0.0114

Gnomad OTH exome AF: 0.00988

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0102 AC: 3764 AN: 370588 Hom.: 3 Cov.: 6 AF XY: 0.00933 AC XY: 1875 AN XY: 200982

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

African (AFR) AF: 0.0191 AC: 207 AN: 10866

American (AMR) AF: 0.0107 AC: 265 AN: 24724

Ashkenazi Jewish (ASJ) AF: 0.00743 AC: 102 AN: 13724

East Asian (EAS) AF: 0.0151 AC: 252 AN: 16734

South Asian (SAS) AF: 0.00308 AC: 145 AN: 47048

European-Finnish (FIN) AF: 0.0117 AC: 187 AN: 16012

Middle Eastern (MID) AF: 0.00643 AC: 10 AN: 1556

European-Non Finnish (NFE) AF: 0.0107 AC: 2364 AN: 220556

Other (OTH) AF: 0.0120 AC: 232 AN: 19368

⚠️ 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: 0.000401 AC: 58 AN: 144494 Hom.: 0 Cov.: 0 AF XY: 0.000425 AC XY: 30 AN XY: 70532

African (AFR) AF: 0.00100 AC: 40 AN: 39856

American (AMR) AF: 0.000342 AC: 5 AN: 14636

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3274

East Asian (EAS) AF: 0.00 AC: 0 AN: 4614

South Asian (SAS) AF: 0.00 AC: 0 AN: 4208

European-Finnish (FIN) AF: 0.000397 AC: 4 AN: 10082

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 250

European-Non Finnish (NFE) AF: 0.000124 AC: 8 AN: 64768

Other (OTH) AF: 0.000501 AC: 1 AN: 1998

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.70
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs199721569; hg19: chr7-33054117;