6-16290617-T-TAC

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_006877.4(GMPR):c.855_856dup(p.Arg286ThrfsTer28) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00192 in 1,613,838 control chromosomes in the GnomAD database, including 5 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0020 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (3 hom.)
• Consequence: GMPR NM_006877.4 frameshift
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 9.32

Genes affected

GMPR (HGNC:4376): (guanosine monophosphate reductase) This gene encodes an enzyme that catalyzes the irreversible and NADPH-dependent reductive deamination of GMP to IMP. The protein also functions in the re-utilization of free intracellular bases and purine nucleosides.[provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 6-16290617-T-TAC is Benign according to our data. Variant chr6-16290617-T-TAC is described in ClinVar as [Likely_benign]. Clinvar id is 731036.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GMPR	NM_006877.4	c.855_856dup	p.Arg286ThrfsTer28	frameshift_variant	8/9	ENST00000259727.5
GMPR	XM_047418656.1			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GMPR	ENST00000259727.5	c.855_856dup	p.Arg286ThrfsTer28	frameshift_variant	8/9	1	NM_006877.4	P1
GMPR	ENST00000540478.1	n.675_676dup		non_coding_transcript_exon_variant	1/2	2
GMPR	ENST00000543191.5	n.350_351dup		non_coding_transcript_exon_variant	3/4	2
GMPR	ENST00000544145.1	n.209_210dup		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes AF: 0.00204 AC: 310 AN: 152084 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00453

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00363

Gnomad OTH AF: 0.000957

GnomAD3 exomes AF: 0.00172 AC: 432 AN: 251434 Hom.: 0 AF XY: 0.00169 AC XY: 230 AN XY: 135878

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00365

Gnomad NFE exome AF: 0.00293

Gnomad OTH exome AF: 0.00212

GnomAD4 exome AF: 0.00191 AC: 2795 AN: 1461636 Hom.: 3 Cov.: 33 AF XY: 0.00188 AC XY: 1368 AN XY: 727090

Gnomad4 AFR exome AF: 0.000239

Gnomad4 AMR exome AF: 0.000268

Gnomad4 ASJ exome AF: 0.000115

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00423

Gnomad4 NFE exome AF: 0.00220

Gnomad4 OTH exome AF: 0.00157

GnomAD4 genome AF: 0.00204 AC: 310 AN: 152202 Hom.: 2 Cov.: 32 AF XY: 0.00196 AC XY: 146 AN XY: 74424

Gnomad4 AFR AF: 0.000241

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00453

Gnomad4 NFE AF: 0.00363

Gnomad4 OTH AF: 0.000947

Alfa AF: 0.00339 Hom.: 3

Bravo AF: 0.00131

EpiCase AF: 0.00158

EpiControl AF: 0.00142

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs147049568; hg19: chr6-16290848;