rs368339361

Variant names:

• chr19-2733023-G-A
• rs368339361
• NM_144564.5:c.673C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-2733023-G-A
• chr19-2733023-G-T
• chr19-2733023-G-C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_144564.5(SLC39A3):​c.673C>T​(p.Pro225Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000121 in 1,605,446 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P225T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: SLC39A3 NM_144564.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0560
• Publications: 0 publications found

Genes affected

SLC39A3 (HGNC:17128): (solute carrier family 39 member 3) Predicted to enable zinc ion transmembrane transporter activity. Predicted to be involved in zinc ion transmembrane transport. Predicted to act upstream of or within several processes, including T cell homeostasis; chordate embryonic development; and zinc ion transport. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000267001 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04022181).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144564.5. 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
	SLC39A3	NM_144564.5	MANE Select	c.673C>T	p.Pro225Ser	missense	Exon 3 of 3	NP_653165.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC39A3	ENST00000269740.9	TSL:1 MANE Select	c.673C>T	p.Pro225Ser	missense	Exon 3 of 3	ENSP00000269740.3	Q9BRY0-1
	ENSG00000267001	ENST00000586572.1	TSL:4	c.210+4025C>T		intron	N/A	ENSP00000467958.1	K7EQS6
	SLC39A3	ENST00000545664.5	TSL:2	c.673C>T	p.Pro225Ser	missense	Exon 3 of 4	ENSP00000445345.1	F5H385

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152154 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

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: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000302 AC: 7 AN: 231954 AF XY: 0.0000313

Gnomad AFR exome AF: 0.00

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: 0.0000692

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000130 AC: 189 AN: 1453292 Hom.: 0 Cov.: 37 AF XY: 0.000130 AC XY: 94 AN XY: 722488

African (AFR) AF: 0.000152 AC: 5 AN: 32984

American (AMR) AF: 0.00 AC: 0 AN: 43960

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25836

East Asian (EAS) AF: 0.00 AC: 0 AN: 39456

South Asian (SAS) AF: 0.00 AC: 0 AN: 85644

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51688

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5736

European-Non Finnish (NFE) AF: 0.000162 AC: 180 AN: 1108020

Other (OTH) AF: 0.0000667 AC: 4 AN: 59968

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152154 Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5 AN XY: 74328

African (AFR) AF: 0.0000241 AC: 1 AN: 41456

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 67996

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000130 Hom.: 0

Bravo AF: 0.0000756

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000117 AC: 1

ExAC AF: 0.00000832 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000594

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	0.099
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	10
DANN	Benign	0.93
DEOGEN2	Benign	0.041	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.056
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.34	N
REVEL	Benign	0.023
Sift	Benign	0.50	T
Sift4G	Benign	0.88	T
Polyphen		0.0	B
Vest4		0.14
MVP		0.18
MPC		0.32
ClinPred		0.032	T
GERP RS		-0.13
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.041
gMVP		0.32
Mutation Taster		=90/10	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: rs368339361; hg19: chr19-2733021;