chr19-2733190-C-T

Variant names:

• chr19-2733190-C-T
• rs140376410
• NM_144564.5:c.506G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_144564.5(SLC39A3):​c.506G>A​(p.Arg169His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0126 in 1,607,586 control chromosomes in the GnomAD database, including 148 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R169C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0075 (11 hom., cov: 33)
  • Exomes 𝑓: 0.013 (137 hom.)
• Consequence: SLC39A3 NM_144564.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 7.39
• Publications: 9 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010228008).
• BP6: Variant 19-2733190-C-T is Benign according to our data. Variant chr19-2733190-C-T is described in ClinVar as Benign. ClinVar VariationId is 770650.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAdExome4 allele frequency = 0.0131 (19059/1455288) while in subpopulation NFE AF = 0.0158 (17546/1109438). AF 95% confidence interval is 0.0156. There are 137 homozygotes in GnomAdExome4. There are 9291 alleles in the male GnomAdExome4 subpopulation. Median coverage is 37. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 11 AR gene

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.506G>A	p.Arg169His	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.506G>A	p.Arg169His	missense	Exon 3 of 3	ENSP00000269740.3	Q9BRY0-1
	ENSG00000267001	ENST00000586572.1	TSL:4	c.210+3858G>A		intron	N/A	ENSP00000467958.1	K7EQS6
	SLC39A3	ENST00000545664.5	TSL:2	c.506G>A	p.Arg169His	missense	Exon 3 of 4	ENSP00000445345.1	F5H385

Frequencies

GnomAD3 genomes AF: 0.00751 AC: 1143 AN: 152180 Hom.: 11 Cov.: 33

Gnomad AFR AF: 0.00277

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00621

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00248

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0131

Gnomad OTH AF: 0.00574

GnomAD2 exomes AF: 0.00708 AC: 1631 AN: 230422 AF XY: 0.00718

Gnomad AFR exome AF: 0.00329

Gnomad AMR exome AF: 0.00531

Gnomad ASJ exome AF: 0.00347

Gnomad EAS exome AF: 0.0000573

Gnomad FIN exome AF: 0.00161

Gnomad NFE exome AF: 0.0116

Gnomad OTH exome AF: 0.00950

GnomAD4 exome AF: 0.0131 AC: 19059 AN: 1455288 Hom.: 137 Cov.: 37 AF XY: 0.0128 AC XY: 9291 AN XY: 723732

African (AFR) AF: 0.00219 AC: 73 AN: 33290

American (AMR) AF: 0.00575 AC: 253 AN: 44006

Ashkenazi Jewish (ASJ) AF: 0.00392 AC: 101 AN: 25762

East Asian (EAS) AF: 0.0000758 AC: 3 AN: 39560

South Asian (SAS) AF: 0.00392 AC: 336 AN: 85746

European-Finnish (FIN) AF: 0.00180 AC: 93 AN: 51652

Middle Eastern (MID) AF: 0.00174 AC: 10 AN: 5744

European-Non Finnish (NFE) AF: 0.0158 AC: 17546 AN: 1109438

Other (OTH) AF: 0.0107 AC: 644 AN: 60090

GnomAD4 genome AF: 0.00751 AC: 1143 AN: 152298 Hom.: 11 Cov.: 33 AF XY: 0.00670 AC XY: 499 AN XY: 74464

African (AFR) AF: 0.00277 AC: 115 AN: 41576

American (AMR) AF: 0.00621 AC: 95 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00248 AC: 12 AN: 4832

European-Finnish (FIN) AF: 0.00113 AC: 12 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0131 AC: 888 AN: 68006

Other (OTH) AF: 0.00568 AC: 12 AN: 2114

Alfa AF: 0.0115 Hom.: 13

Bravo AF: 0.00799

ESP6500AA AF: 0.00353 AC: 15

ESP6500EA AF: 0.0117 AC: 97

ExAC AF: 0.00667 AC: 789

Asia WGS AF: 0.00173 AC: 6 AN: 3474

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.38	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.89	D
MetaRNN	Benign	0.010	T
MetaSVM	Benign	-0.78	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		7.4
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.15
Sift	Benign	0.10	T
Sift4G	Benign	0.087	T
Polyphen		0.97	D
Vest4		0.84
MVP		0.61
MPC		1.1
ClinPred		0.021	T
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.26
gMVP		0.83
Mutation Taster		=87/13	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: rs140376410; hg19: chr19-2733188; COSMIC: COSV108071779; COSMIC: COSV108071779;