9-113256221-C-G

Position:

• chr9-113256221-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001859.4(SLC31A1):​c.73C>G​(p.Pro25Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00411 in 1,613,598 control chromosomes in the GnomAD database, including 248 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.022 (129 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (119 hom.)
• Consequence: SLC31A1 NM_001859.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.314

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]

LOC107987119 (HGNC:):

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0014228523).
• BP6: Variant 9-113256221-C-G is Benign according to our data. Variant chr9-113256221-C-G is described in ClinVar as [Benign]. Clinvar id is 713723.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.074 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC31A1	NM_001859.4	c.73C>G	p.Pro25Ala	missense_variant	2/5	ENST00000374212.5	NP_001850.1
LOC107987119	XR_007061737.1	n.149+234G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC31A1	ENST00000374212.5	c.73C>G	p.Pro25Ala	missense_variant	2/5	1	NM_001859.4	ENSP00000363329	P1
CDC26	ENST00000490408.5	n.495-178G>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0217 AC: 3301 AN: 152088 Hom.: 129 Cov.: 32

Gnomad AFR AF: 0.0764

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00583

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.0134

GnomAD3 exomes AF: 0.00581 AC: 1460 AN: 251262 Hom.: 53 AF XY: 0.00440 AC XY: 598 AN XY: 135780

Gnomad AFR exome AF: 0.0796

Gnomad AMR exome AF: 0.00356

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000203

Gnomad OTH exome AF: 0.00245

GnomAD4 exome AF: 0.00228 AC: 3332 AN: 1461392 Hom.: 119 Cov.: 31 AF XY: 0.00192 AC XY: 1398 AN XY: 726996

Gnomad4 AFR exome AF: 0.0796

Gnomad4 AMR exome AF: 0.00407

Gnomad4 ASJ exome AF: 0.000115

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000325

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000149

Gnomad4 OTH exome AF: 0.00464

GnomAD4 genome AF: 0.0217 AC: 3303 AN: 152206 Hom.: 129 Cov.: 32 AF XY: 0.0210 AC XY: 1562 AN XY: 74428

Gnomad4 AFR AF: 0.0762

Gnomad4 AMR AF: 0.00582

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000323

Gnomad4 OTH AF: 0.0133

Alfa AF: 0.00684 Hom.: 9

Bravo AF: 0.0246

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0751 AC: 331

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00725 AC: 880

Asia WGS AF: 0.00549 AC: 20 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	1.6
DANN	Benign	0.85
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.48	T
MetaRNN	Benign	0.0014	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.5	L
MutationTaster	Benign	0.64	N;N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.62	N
REVEL	Benign	0.063
Sift	Benign	0.73	T
Sift4G	Benign	0.85	T
Polyphen		0.018	B
Vest4		0.19
MVP		0.38
MPC		0.47
ClinPred		0.0076	T
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.026
gMVP		0.54

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: rs2233915; hg19: chr9-116018501;