NM_018375.5:c.833C>T

Variant names:

• chr14-69458502-C-T
• rs200562708
• NM_018375.5:c.833C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018375.5(SLC39A9):​c.833C>T​(p.Thr278Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000297 in 1,614,252 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000026 (1 hom.)
• Consequence: SLC39A9 NM_018375.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0780
• Publications: 1 publications found

Genes affected

SLC39A9 (HGNC:20182): (solute carrier family 39 member 9) Predicted to enable metal ion transmembrane transporter activity. Predicted to be involved in transmembrane transport and zinc ion transport. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0725044).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018375.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC39A9	NM_018375.5	MANE Select	c.833C>T	p.Thr278Met	missense	Exon 7 of 7	NP_060845.2
	SLC39A9	NM_001252148.2		c.764C>T	p.Thr255Met	missense	Exon 6 of 6	NP_001239077.1	Q9NUM3-2
	SLC39A9	NM_001330185.2		c.635C>T	p.Thr212Met	missense	Exon 6 of 6	NP_001317114.1	M0QX28

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC39A9	ENST00000336643.10	TSL:1 MANE Select	c.833C>T	p.Thr278Met	missense	Exon 7 of 7	ENSP00000336887.5	Q9NUM3-1
	SLC39A9	ENST00000557046.1	TSL:1	c.764C>T	p.Thr255Met	missense	Exon 6 of 6	ENSP00000451833.1	Q9NUM3-2
	SLC39A9	ENST00000556605.5	TSL:1	c.693+2636C>T		intron	N/A	ENSP00000452385.1	Q9NUM3-3

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152244 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000398 AC: 10 AN: 251390 AF XY: 0.0000368

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000616

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000260 AC: 38 AN: 1461890 Hom.: 1 Cov.: 32 AF XY: 0.0000289 AC XY: 21 AN XY: 727246

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000191 AC: 5 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000261 AC: 29 AN: 1112008

Other (OTH) AF: 0.0000497 AC: 3 AN: 60396

GnomAD4 genome AF: 0.0000656 AC: 10 AN: 152362 Hom.: 0 Cov.: 32 AF XY: 0.0000671 AC XY: 5 AN XY: 74502

African (AFR) AF: 0.0000962 AC: 4 AN: 41584

American (AMR) AF: 0.00 AC: 0 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.0000869 Hom.: 0

Bravo AF: 0.0000756

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000576 AC: 7

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	16
DANN	Benign	0.95
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.14	N
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.073	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.078
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.13
Sift	Benign	0.059	T
Sift4G	Uncertain	0.031	D
Polyphen		0.70	P
Vest4		0.19
MVP		0.11
MPC		1.1
ClinPred		0.025	T
GERP RS		0.46
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.021
gMVP		0.36
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs200562708; hg19: chr14-69925219; COSMIC: COSV50362184;