19-2738354-A-T

Variant names:

• chr19-2738354-A-T
• rs4806874
• NM_144564.5:c.-122-975T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_144564.5(SLC39A3):​c.-122-975T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,900 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 30)
• Consequence: SLC39A3 NM_144564.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0520
• Publications: 23 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC39A3	NM_144564.5	c.-122-975T>A		intron_variant	Intron 1 of 2	ENST00000269740.9	NP_653165.2
SLC39A3	NM_213568.2	c.-122-975T>A		intron_variant	Intron 1 of 1		NP_998733.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC39A3	ENST00000269740.9	c.-122-975T>A		intron_variant	Intron 1 of 2	1	NM_144564.5	ENSP00000269740.3
ENSG00000267001	ENST00000586572.1	c.-122-975T>A		intron_variant	Intron 1 of 2	4		ENSP00000467958.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151900 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151900 Hom.: 0 Cov.: 30 AF XY: 0.0000135 AC XY: 1 AN XY: 74178

African (AFR) AF: 0.00 AC: 0 AN: 41322

American (AMR) AF: 0.00 AC: 0 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10548

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67978

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 30295

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.47
PhyloP100		0.052

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: rs4806874; hg19: chr19-2738352;