9-113258856-C-T

Variant names:

• chr9-113258856-C-T
• rs2233916
• NM_001859.4:c.365C>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001859.4(SLC31A1):​c.365C>T​(p.Thr122Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T122S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC31A1 NM_001859.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.25

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC31A1	NM_001859.4	c.365C>T	p.Thr122Ile	missense_variant	Exon 4 of 5	ENST00000374212.5	NP_001850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC31A1	ENST00000374212.5	c.365C>T	p.Thr122Ile	missense_variant	Exon 4 of 5	1	NM_001859.4	ENSP00000363329.4
CDC26	ENST00000490408.5	n.401-2308G>A		intron_variant	Intron 3 of 4	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.071	D
MetaRNN	Uncertain	0.72	D
MetaSVM	Uncertain	0.074	D
MutationAssessor	Benign	2.0	M
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.87	N
REVEL	Uncertain	0.46
Sift	Benign	0.24	T
Sift4G	Benign	0.36	T
Polyphen		0.96	D
Vest4		0.82
MutPred		0.40		Loss of relative solvent accessibility (P = 0.0404);
MVP		0.51
MPC		0.91
ClinPred		0.82	D
GERP RS		5.8
Varity_R		0.14
gMVP		0.74

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: rs2233916; hg19: chr9-116021136;