chr19-2733010-G-A

Variant names:

• chr19-2733010-G-A
• rs1177311033
• NM_144564.5:c.686C>T

Variant summary

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

The NM_144564.5(SLC39A3):​c.686C>T​(p.Ala229Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000375 in 1,599,014 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/22 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. A229T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: SLC39A3 NM_144564.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.67
• 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: 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_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.686C>T	p.Ala229Val	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.686C>T	p.Ala229Val	missense	Exon 3 of 3	ENSP00000269740.3	Q9BRY0-1
	ENSG00000267001	ENST00000586572.1	TSL:4	c.210+4038C>T		intron	N/A	ENSP00000467958.1	K7EQS6
	SLC39A3	ENST00000545664.5	TSL:2	c.686C>T	p.Ala229Val	missense	Exon 3 of 4	ENSP00000445345.1	F5H385

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152046 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000346 AC: 5 AN: 1446968 Hom.: 0 Cov.: 37 AF XY: 0.00000418 AC XY: 3 AN XY: 718500

African (AFR) AF: 0.0000306 AC: 1 AN: 32710

American (AMR) AF: 0.00 AC: 0 AN: 43302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25576

East Asian (EAS) AF: 0.0000255 AC: 1 AN: 39286

South Asian (SAS) AF: 0.00 AC: 0 AN: 85216

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51480

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5714

European-Non Finnish (NFE) AF: 9.06e-7 AC: 1 AN: 1104088

Other (OTH) AF: 0.0000336 AC: 2 AN: 59596

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152046 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74266

African (AFR) AF: 0.00 AC: 0 AN: 41410

American (AMR) AF: 0.00 AC: 0 AN: 15278

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5150

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67984

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.30
BayesDel_addAF	Benign	0.0059	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.046	T
Eigen	Benign	0.055
Eigen_PC	Benign	0.16
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.63	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		7.7
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	0.97	N
REVEL	Benign	0.21
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.80	P
Vest4		0.73
MutPred		0.67		Loss of disorder (P = 0.0835)
MVP		0.62
MPC		0.34
ClinPred		0.73	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.21
gMVP		0.61
Mutation Taster		=61/39	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: rs1177311033; hg19: chr19-2733008; COSMIC: COSV54118806; COSMIC: COSV54118806;