12-68686678-C-T

Position:

• chr12-68686678-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The ENST00000502102.2(NUP107-DT):​n.822+256G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0104 in 211,878 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0096 (14 hom., cov: 33)
  • Exomes 𝑓: 0.012 (9 hom.)
• Consequence: NUP107-DT ENST00000502102.2 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.22

Genes affected

NUP107-DT (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 12-68686678-C-T is Benign according to our data. Variant chr12-68686678-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1320404.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 14 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC100507250	NR_038930.1	n.123+59G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUP107-DT	ENST00000502102.2	n.822+256G>A		intron_variant		1
NUP107-DT	ENST00000433116.2	n.101+59G>A		intron_variant		2
NUP107-DT	ENST00000500695.2	n.123+59G>A		intron_variant		5
NUP107-DT	ENST00000690517.1	n.140+59G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.00963 AC: 1466 AN: 152246 Hom.: 14 Cov.: 33

Gnomad AFR AF: 0.00273

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.00530

Gnomad ASJ AF: 0.0107

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.00538

Gnomad FIN AF: 0.0137

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0151

Gnomad OTH AF: 0.0105

GnomAD4 exome AF: 0.0124 AC: 739 AN: 59514 Hom.: 9 AF XY: 0.0127 AC XY: 389 AN XY: 30662

Gnomad4 AFR exome AF: 0.00186

Gnomad4 AMR exome AF: 0.00736

Gnomad4 ASJ exome AF: 0.0137

Gnomad4 EAS exome AF: 0.000322

Gnomad4 SAS exome AF: 0.00539

Gnomad4 FIN exome AF: 0.0147

Gnomad4 NFE exome AF: 0.0150

Gnomad4 OTH exome AF: 0.0133

GnomAD4 genome AF: 0.00962 AC: 1465 AN: 152364 Hom.: 14 Cov.: 33 AF XY: 0.00921 AC XY: 686 AN XY: 74506

Gnomad4 AFR AF: 0.00272

Gnomad4 AMR AF: 0.00529

Gnomad4 ASJ AF: 0.0107

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.00538

Gnomad4 FIN AF: 0.0137

Gnomad4 NFE AF: 0.0151

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.00587 Hom.: 1

Bravo AF: 0.00909

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 23, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	4.7
DANN	Benign	0.83

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs146624314; hg19: chr12-69080458;