3-48301594-C-CCCCTCGGAAGCCGGCCTGGGCGCCCTCGGAAGCCGGCCTGGGCGCCCTCGGAAGCCGGCCTGGGCG

Variant names:

• chr3-48301594-C-CCCCTCGGAAGCCGGCCTGGGCGCCCTCGGAAGCCGGCCTGGGCGCCCTCGGAAGCCGGCCTGGGCG
• ENST00000451657.6:c.-250_-249insCGCCCAGGCCGGCTTCCGAGGGCGCCCAGGCCGGCTTCCGAGGGCGCCCAGGCCGGCTTCCGAGGG

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The ENST00000451657.6(NME6):​c.-250_-249insCGCCCAGGCCGGCTTCCGAGGGCGCCCAGGCCGGCTTCCGAGGGCGCCCAGGCCGGCTTCCGAGGG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0034 (15 hom., cov: 33)
  • Exomes 𝑓: 0.000061 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NME6 ENST00000451657.6 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.629

Genes affected

NME6 (HGNC:20567): (NME/NM23 nucleoside diphosphate kinase 6) Nucleoside diphosphate (NDP) kinases (EC 2.7.4.6), such as NME6, are ubiquitous enzymes that catalyze transfer of gamma-phosphates, via a phosphohistidine intermediate, between nucleoside and dioxynucleoside tri- and diphosphates (Mehus et al., 1999 [PubMed 10453732]).[supplied by OMIM, Jul 2010]

ENSG00000289043 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP6: Variant 3-48301594-C-CCCCTCGGAAGCCGGCCTGGGCGCCCTCGGAAGCCGGCCTGGGCGCCCTCGGAAGCCGGCCTGGGCG is Benign according to our data. Variant chr3-48301594-C-CCCCTCGGAAGCCGGCCTGGGCGCCCTCGGAAGCCGGCCTGGGCGCCCTCGGAAGCCGGCCTGGGCG is described in ClinVar as [Likely_benign]. Clinvar id is 2653785.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NME6	NM_001308426.2	c.-250_-249insCGCCCAGGCCGGCTTCCGAGGGCGCCCAGGCCGGCTTCCGAGGGCGCCCAGGCCGGCTTCCGAGGG		upstream_gene_variant		ENST00000442597.6	NP_001295355.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NME6	ENST00000442597.6	c.-250_-249insCGCCCAGGCCGGCTTCCGAGGGCGCCCAGGCCGGCTTCCGAGGGCGCCCAGGCCGGCTTCCGAGGG		upstream_gene_variant		1	NM_001308426.2	ENSP00000406642.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 507 AN: 149202 Hom.: 15 Cov.: 33 FAILED QC

Gnomad AFR AF: 0.00947

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00298

Gnomad ASJ AF: 0.00997

Gnomad EAS AF: 0.000195

Gnomad SAS AF: 0.00150

Gnomad FIN AF: 0.000284

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000546

Gnomad OTH AF: 0.00387

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000608 AC: 66 AN: 1085018 Hom.: 0 Cov.: 31 AF XY: 0.0000717 AC XY: 37 AN XY: 516342

Gnomad4 AFR exome AF: 0.000849

Gnomad4 AMR exome AF: 0.000221

Gnomad4 ASJ exome AF: 0.00146

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000605

Gnomad4 FIN exome AF: 0.0000937

Gnomad4 NFE exome AF: 0.0000153

Gnomad4 OTH exome AF: 0.000185

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00340 AC: 507 AN: 149298 Hom.: 15 Cov.: 33 AF XY: 0.00333 AC XY: 243 AN XY: 72990

Gnomad4 AFR AF: 0.00947

Gnomad4 AMR AF: 0.00297

Gnomad4 ASJ AF: 0.00997

Gnomad4 EAS AF: 0.000196

Gnomad4 SAS AF: 0.00128

Gnomad4 FIN AF: 0.000284

Gnomad4 NFE AF: 0.000546

Gnomad4 OTH AF: 0.00383

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Apr 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ENSG00000289043: BS2 -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-48343084;