12-56231261-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_173596.3(SLC39A5):c.-14T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.998 in 1,587,226 control chromosomes in the GnomAD database, including 790,145 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.99 (74670 hom., cov: 30)
  • Exomes 𝑓: 1.0 (715475 hom.)
• Consequence: SLC39A5 NM_173596.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.865

Genes affected

SLC39A5 (HGNC:20502): (solute carrier family 39 member 5) The protein encoded by this gene belongs to the ZIP family of zinc transporters that transport zinc into cells from outside, and play a crucial role in controlling intracellular zinc levels. Zinc is an essential cofactor for many enzymes and proteins involved in gene transcription, growth, development and differentiation. Mutations in this gene have been associated with autosomal dominant high myopia (MYP24). Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2014]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 12-56231261-T-C is Benign according to our data. Variant chr12-56231261-T-C is described in ClinVar as [Benign]. Clinvar id is 1333138.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC39A5	NM_173596.3	c.-14T>C		5_prime_UTR_variant	4/13	ENST00000454355.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC39A5	ENST00000454355.7	c.-14T>C		5_prime_UTR_variant	4/13	1	NM_173596.3	P1

Frequencies

GnomAD3 genomes AF: 0.990 AC: 150631 AN: 152076 Hom.: 74612 Cov.: 30

Gnomad AFR AF: 0.969

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.994

Gnomad ASJ AF: 0.988

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.997

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.997

GnomAD3 exomes AF: 0.997 AC: 228873 AN: 229634 Hom.: 114060 AF XY: 0.997 AC XY: 124135 AN XY: 124478

Gnomad AFR exome AF: 0.968

Gnomad AMR exome AF: 0.997

Gnomad ASJ exome AF: 0.986

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 0.999

Gnomad OTH exome AF: 0.997

GnomAD4 exome AF: 0.999 AC: 1432971 AN: 1435032 Hom.: 715475 Cov.: 45 AF XY: 0.999 AC XY: 710226 AN XY: 711192

Gnomad4 AFR exome AF: 0.970

Gnomad4 AMR exome AF: 0.997

Gnomad4 ASJ exome AF: 0.987

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.996

GnomAD4 genome AF: 0.990 AC: 150748 AN: 152194 Hom.: 74670 Cov.: 30 AF XY: 0.991 AC XY: 73705 AN XY: 74392

Gnomad4 AFR AF: 0.969

Gnomad4 AMR AF: 0.994

Gnomad4 ASJ AF: 0.988

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 1.00

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 1.00

Gnomad4 OTH AF: 0.997

Alfa AF: 0.997 Hom.: 65261

Bravo AF: 0.989

Asia WGS AF: 0.998 AC: 3470 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Myopia 24, autosomal dominant Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	4.1
Dann	Benign	0.58
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs1274497; hg19: chr12-56625045;