NM_144564.5:c.-122-975T>C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_144564.5(SLC39A3):​c.-122-975T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 151,954 control chromosomes in the GnomAD database, including 18,270 homozygotes. 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 0.45 (18270 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.743 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC39A3	NM_144564.5	c.-122-975T>C		intron_variant	Intron 1 of 2	ENST00000269740.9	NP_653165.2
SLC39A3	NM_213568.2	c.-122-975T>C		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>C		intron_variant	Intron 1 of 2	1	NM_144564.5	ENSP00000269740.3
ENSG00000267001	ENST00000586572.1	c.-122-975T>C		intron_variant	Intron 1 of 2	4		ENSP00000467958.1

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68349 AN: 151836 Hom.: 18223 Cov.: 30

Gnomad AFR AF: 0.750

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.563

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.439

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

GnomAD4 genome AF: 0.450 AC: 68445 AN: 151954 Hom.: 18270 Cov.: 30 AF XY: 0.456 AC XY: 33902 AN XY: 74274

African (AFR) AF: 0.750 AC: 31063 AN: 41422

American (AMR) AF: 0.365 AC: 5572 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 1146 AN: 3466

East Asian (EAS) AF: 0.563 AC: 2913 AN: 5174

South Asian (SAS) AF: 0.488 AC: 2358 AN: 4828

European-Finnish (FIN) AF: 0.342 AC: 3602 AN: 10540

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.301 AC: 20439 AN: 67950

Other (OTH) AF: 0.439 AC: 924 AN: 2104

Alfa AF: 0.355 Hom.: 30295

Bravo AF: 0.462

Asia WGS AF: 0.554 AC: 1928 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.9
DANN	Benign	0.38
PhyloP100		0.052
Mutation Taster		=100/0	polymorphism (auto)

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;