NM_012319.4:c.1259C>G

Variant names:

• chr18-36122152-G-C
• rs200789263
• NM_012319.4:c.1259C>G

Variant summary

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

The NM_012319.4(SLC39A6):​c.1259C>G​(p.Ser420Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,734 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. S420F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLC39A6 NM_012319.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.26
• Publications: 0 publications found

Genes affected

SLC39A6 (HGNC:18607): (solute carrier family 39 member 6) Zinc is an essential cofactor for hundreds of enzymes. It is involved in protein, nucleic acid, carbohydrate, and lipid metabolism, as well as in the control of gene transcription, growth, development, and differentiation. SLC39A6 belongs to a subfamily of proteins that show structural characteristics of zinc transporters (Taylor and Nicholson, 2003 [PubMed 12659941]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012319.4. 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
	SLC39A6	NM_012319.4	MANE Select	c.1259C>G	p.Ser420Cys	missense	Exon 5 of 10	NP_036451.4
	SLC39A6	NM_001099406.2		c.434C>G	p.Ser145Cys	missense	Exon 4 of 8	NP_001092876.1	Q13433-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC39A6	ENST00000269187.10	TSL:2 MANE Select	c.1259C>G	p.Ser420Cys	missense	Exon 5 of 10	ENSP00000269187.4	Q13433-1
	SLC39A6	ENST00000440549.6	TSL:1	c.434C>G	p.Ser145Cys	missense	Exon 4 of 8	ENSP00000401139.1	Q13433-2
	SLC39A6	ENST00000590986.5	TSL:5	c.1259C>G	p.Ser420Cys	missense	Exon 5 of 10	ENSP00000465915.1	Q13433-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461734 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727180

African (AFR) AF: 0.00 AC: 0 AN: 33472

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

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

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111894

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Uncertain	0.037	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.035	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Uncertain	-0.20	T
MutationAssessor	Benign	1.8	L
PhyloP100		6.3
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-2.1	N
REVEL	Uncertain	0.32
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.028	D
Polyphen		1.0	D
Vest4		0.60
MutPred		0.73		Loss of disorder (P = 0.0204)
MVP		0.89
MPC		0.43
ClinPred		0.95	D
GERP RS		5.2
PromoterAI		0.0045	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.25
gMVP		0.39
Mutation Taster		=74/26	polymorphism

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

Other links and lift over

dbSNP: rs200789263; hg19: chr18-33702115;