18-36114157-G-T

Variant names:

• chr18-36114157-G-T
• NM_012319.4:c.1783C>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_012319.4(SLC39A6):​c.1783C>A​(p.Leu595Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC39A6 NM_012319.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.37

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34858522).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC39A6	NM_012319.4	c.1783C>A	p.Leu595Met	missense_variant	Exon 7 of 10	ENST00000269187.10	NP_036451.4
SLC39A6	NM_001099406.2	c.958C>A	p.Leu320Met	missense_variant	Exon 6 of 8		NP_001092876.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC39A6	ENST00000269187.10	c.1783C>A	p.Leu595Met	missense_variant	Exon 7 of 10	2	NM_012319.4	ENSP00000269187.4
SLC39A6	ENST00000440549.6	c.958C>A	p.Leu320Met	missense_variant	Exon 6 of 8	1		ENSP00000401139.1
SLC39A6	ENST00000590986.5	c.1783C>A	p.Leu595Met	missense_variant	Exon 7 of 10	5		ENSP00000465915.1
SLC39A6	ENST00000586829.1	c.484C>A	p.Leu162Met	missense_variant	Exon 3 of 5	3		ENSP00000467724.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 43

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Benign	-0.046	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.057	T;T;.;.
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.60	D
LIST_S2	Uncertain	0.87	.;D;T;T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.35	T;T;T;T
MetaSVM	Benign	-0.74	T
MutationAssessor	Uncertain	2.2	M;M;.;.
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.2	N;.;N;.
REVEL	Benign	0.24
Sift	Uncertain	0.0070	D;.;D;.
Sift4G	Benign	0.12	T;T;T;T
Polyphen		0.97	D;D;D;.
Vest4		0.57
MutPred		0.47		Loss of catalytic residue at L595 (P = 0.0075);Loss of catalytic residue at L595 (P = 0.0075);.;.;
MVP		0.49
MPC		2.1
ClinPred		0.83	D
GERP RS		-0.77
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.22
gMVP		0.72

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-33694120;