rs10759637

chr9-113262744-A-Cchr9-113262744-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001859.4(SLC31A1):c.*2271A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 152,490 control chromosomes in the GnomAD database, including 17,438 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.47 (17384 hom., cov: 33)
  • Exomes 𝑓: 0.50 (54 hom.)
• Consequence: SLC31A1 NM_001859.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.565

Genes affected

SLC31A1 (HGNC:11016): (solute carrier family 31 member 1) The protein encoded by this gene is a high-affinity copper transporter found in the cell membrane. The encoded protein functions as a homotrimer to effect the uptake of dietary copper. [provided by RefSeq, Aug 2011]

CDC26 (HGNC:17839): (cell division cycle 26) The protein encoded by this gene is highly similar to Saccharomyces cerevisiae Cdc26, a component of cell cycle anaphase-promoting complex (APC). APC is composed of a group of highly conserved proteins and functions as a cell cycle-regulated ubiquitin-protein ligase. APC thus is responsible for the cell cycle regulated proteolysis of various proteins. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC31A1	NM_001859.4	c.*2271A>C		3_prime_UTR_variant	5/5	ENST00000374212.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC31A1	ENST00000374212.5	c.*2271A>C		3_prime_UTR_variant	5/5	1	NM_001859.4	P1
CDC26	ENST00000490408.5	n.401-6196T>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.473 AC: 71881 AN: 151946 Hom.: 17368 Cov.: 33

Gnomad AFR AF: 0.541

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.527

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.448

GnomAD4 exome AF: 0.498 AC: 212 AN: 426 Hom.: 54 Cov.: 0 AF XY: 0.511 AC XY: 134 AN XY: 262

Gnomad4 FIN exome AF: 0.498

Gnomad4 NFE exome AF: 0.583

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.473 AC: 71950 AN: 152064 Hom.: 17384 Cov.: 33 AF XY: 0.477 AC XY: 35435 AN XY: 74332

Gnomad4 AFR AF: 0.541

Gnomad4 AMR AF: 0.417

Gnomad4 ASJ AF: 0.527

Gnomad4 EAS AF: 0.481

Gnomad4 SAS AF: 0.588

Gnomad4 FIN AF: 0.474

Gnomad4 NFE AF: 0.433

Gnomad4 OTH AF: 0.451

Alfa AF: 0.442 Hom.: 24846

Bravo AF: 0.473

Asia WGS AF: 0.565 AC: 1960 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	7.0
Dann	Benign	0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs10759637; hg19: chr9-116025024;