X-75156585-C-T

Variant names:

• chrX-75156585-C-T
• rs5981325
• NM_001363821.1:c.-379+35C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_001363821.1(UPRT):​c.-379+35C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.92 (33170 hom., 29415 hem., cov: 22)
  • Exomes 𝑓: 0.99 (101479 hom. 106321 hem.)
  • Failed GnomAD Quality Control
• Consequence: UPRT NM_001363821.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.361
• Publications: 3 publications found

Genes affected

UPRT (HGNC:28334): (uracil phosphoribosyltransferase homolog) This gene encodes uracil phosphoribosyltransferase, which catalyzes the conversion of uracil and 5-phosphoribosyl-1-R-diphosphate to uridine monophosphate (UMP). This reaction is an important part of nucleotide metabolism, specifically the pyrimidine salvage pathway. The enzyme localizes to the nucleus and cytoplasm. The protein is a potential target for rational design of drugs to treat parasitic infections and cancer. [provided by RefSeq, Nov 2009]

ABCB7 (HGNC:48): (ATP binding cassette subfamily B member 7) The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance as well as antigen presentation. This gene encodes a half-transporter involved in the transport of heme from the mitochondria to the cytosol. With iron/sulfur cluster precursors as its substrates, this protein may play a role in metal homeostasis. Mutations in this gene have been associated with mitochondrial iron accumulation and isodicentric (X)(q13) and sideroblastic anemia. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2012]

ABCB7 Gene-Disease associations (from GenCC):

• X-linked sideroblastic anemia with ataxia

  Inheritance: XL, XLR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, Illumina, Labcorp Genetics (formerly Invitae), G2P
• mitochondrial disease

  Inheritance: XL Classification: MODERATE Submitted by: ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant X-75156585-C-T is Benign according to our data. Variant chrX-75156585-C-T is described in ClinVar as Benign. ClinVar VariationId is 1260246.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363821.1. 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
	UPRT	NM_001363821.1		c.-379+35C>T		intron	N/A	NP_001350750.1	E9PSD7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB7	ENST00000526404.2	TSL:5	c.-1+77G>A		intron	N/A	ENSP00000432813.2	E9PNQ5
	UPRT	ENST00000652605.1		c.-737+35C>T		intron	N/A	ENSP00000498525.1	A0A494C0H3

Frequencies

GnomAD3 genomes AF: 0.917 AC: 100480 AN: 109568 Hom.: 33173 Cov.: 22

Gnomad AFR AF: 0.713

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.966

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.967

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.934

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.988 AC: 311599 AN: 315497 Hom.: 101479 AF XY: 0.992 AC XY: 106321 AN XY: 107203

African (AFR) AF: 0.716 AC: 7474 AN: 10436

American (AMR) AF: 0.984 AC: 23921 AN: 24302

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 11914 AN: 11914

East Asian (EAS) AF: 1.00 AC: 15594 AN: 15594

South Asian (SAS) AF: 0.999 AC: 36000 AN: 36036

European-Finnish (FIN) AF: 1.00 AC: 16259 AN: 16259

Middle Eastern (MID) AF: 0.989 AC: 2500 AN: 2528

European-Non Finnish (NFE) AF: 1.00 AC: 180482 AN: 180570

Other (OTH) AF: 0.977 AC: 17455 AN: 17858

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.917 AC: 100527 AN: 109622 Hom.: 33170 Cov.: 22 AF XY: 0.922 AC XY: 29415 AN XY: 31888

African (AFR) AF: 0.713 AC: 21410 AN: 30010

American (AMR) AF: 0.966 AC: 9871 AN: 10223

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2627 AN: 2627

East Asian (EAS) AF: 1.00 AC: 3460 AN: 3460

South Asian (SAS) AF: 1.00 AC: 2515 AN: 2516

European-Finnish (FIN) AF: 1.00 AC: 5624 AN: 5624

Middle Eastern (MID) AF: 0.963 AC: 210 AN: 218

European-Non Finnish (NFE) AF: 0.999 AC: 52738 AN: 52775

Other (OTH) AF: 0.935 AC: 1394 AN: 1491

Alfa AF: 0.912 Hom.: 10952

Bravo AF: 0.906

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.4
DANN	Benign	0.56
PhyloP100		-0.36
PromoterAI		-0.0080	Neutral

Splicing

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

Other links and lift over

dbSNP: rs5981325; hg19: chrX-74376420;