19-2733190-C-T

Position:

• chr19-2733190-C-T

Variant summary

Our verdict is Benign. Variant got -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 (★★).

• 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

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

Verdict is Benign. Variant got -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 id 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. gnomad4_exome 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 gnomad4_exome. There are 9291 alleles in male gnomad4_exome subpopulation. Median coverage is 37. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC39A3	NM_144564.5	c.506G>A	p.Arg169His	missense_variant	3/3	ENST00000269740.9	NP_653165.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC39A3	ENST00000269740.9	c.506G>A	p.Arg169His	missense_variant	3/3	1	NM_144564.5	ENSP00000269740.3
ENSG00000267001	ENST00000586572.1	c.210+3858G>A		intron_variant		4		ENSP00000467958.1
SLC39A3	ENST00000545664.5	c.506G>A	p.Arg169His	missense_variant	3/4	2		ENSP00000445345.1

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

GnomAD3 exomes AF: 0.00708 AC: 1631 AN: 230422 Hom.: 11 AF XY: 0.00718 AC XY: 914 AN XY: 127380

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 SAS exome AF: 0.00408

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

Gnomad4 AFR exome AF: 0.00219

Gnomad4 AMR exome AF: 0.00575

Gnomad4 ASJ exome AF: 0.00392

Gnomad4 EAS exome AF: 0.0000758

Gnomad4 SAS exome AF: 0.00392

Gnomad4 FIN exome AF: 0.00180

Gnomad4 NFE exome AF: 0.0158

Gnomad4 OTH exome AF: 0.0107

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

Gnomad4 AFR AF: 0.00277

Gnomad4 AMR AF: 0.00621

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00248

Gnomad4 FIN AF: 0.00113

Gnomad4 NFE AF: 0.0131

Gnomad4 OTH AF: 0.00568

Alfa AF: 0.0119 Hom.: 9

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

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Oct 10, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

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;D
MetaRNN	Benign	0.010	T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Uncertain	2.3	.;M
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-2.8	D;D
REVEL	Benign	0.15
Sift	Benign	0.10	T;T
Sift4G	Benign	0.087	T;T
Polyphen		0.97	D;P
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

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

Publications

LitVar

Other links and lift over

dbSNP: rs140376410; hg19: chr19-2733188;