rs7242481

Variant names:

• chr18-36129254-G-A
• rs7242481
• NM_012319.4:c.-150C>T

Variant summary

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

The NM_012319.4(SLC39A6):​c.-150C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 155,164 control chromosomes in the GnomAD database, including 9,234 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 0.34 (9075 hom., cov: 33)
  • Exomes 𝑓: 0.29 (159 hom.)
• Consequence: SLC39A6 NM_012319.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.88
• Publications: 25 publications found

Genes affected

SLC39A6 (HGNC:18607): (solute carrier family 39 member 6) Zinc is an essential cofactor for hundreds of enzymes. It is involved in protein, nucleic acid, carbohydrate, and lipid metabolism, as well as in the control of gene transcription, growth, development, and differentiation. SLC39A6 belongs to a subfamily of proteins that show structural characteristics of zinc transporters (Taylor and Nicholson, 2003 [PubMed 12659941]).[supplied by OMIM, Mar 2008]

ENSG00000288917 (HGNC:):

ELP2 (HGNC:18248): (elongator acetyltransferase complex subunit 2) The protein encoded by this gene is a core subunit of the elongator complex, a histone acetyltransferase complex that associates with RNA polymerase II. In addition to histone acetylation, the encoded protein effects transcriptional elongation and may help remodel chromatin. [provided by RefSeq, May 2016]

ELP2 Gene-Disease associations (from GenCC):

• intellectual disability, autosomal recessive 58

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012319.4. 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
	SLC39A6	NM_012319.4	MANE Select	c.-150C>T		5_prime_UTR	Exon 1 of 10	NP_036451.4
	SLC39A6	NM_001099406.2		c.-177C>T		5_prime_UTR	Exon 1 of 8	NP_001092876.1	Q13433-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC39A6	ENST00000269187.10	TSL:2 MANE Select	c.-150C>T		5_prime_UTR	Exon 1 of 10	ENSP00000269187.4	Q13433-1
	SLC39A6	ENST00000440549.6	TSL:1	c.-177C>T		5_prime_UTR	Exon 1 of 8	ENSP00000401139.1	Q13433-2
	SLC39A6	ENST00000590986.5	TSL:5	c.-163C>T		5_prime_UTR	Exon 1 of 10	ENSP00000465915.1	Q13433-1

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52338 AN: 152016 Hom.: 9078 Cov.: 33

Gnomad AFR AF: 0.351

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.350

GnomAD4 exome AF: 0.290 AC: 879 AN: 3026 Hom.: 159 Cov.: 0 AF XY: 0.277 AC XY: 443 AN XY: 1600

African (AFR) AF: 0.625 AC: 5 AN: 8

American (AMR) AF: 0.362 AC: 184 AN: 508

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8

East Asian (EAS) AF: 0.179 AC: 5 AN: 28

South Asian (SAS) AF: 0.165 AC: 82 AN: 496

European-Finnish (FIN) AF: 0.275 AC: 11 AN: 40

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.307 AC: 568 AN: 1848

Other (OTH) AF: 0.261 AC: 23 AN: 88

GnomAD4 genome AF: 0.344 AC: 52349 AN: 152138 Hom.: 9075 Cov.: 33 AF XY: 0.342 AC XY: 25431 AN XY: 74356

African (AFR) AF: 0.351 AC: 14573 AN: 41542

American (AMR) AF: 0.360 AC: 5509 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 1330 AN: 3470

East Asian (EAS) AF: 0.196 AC: 1005 AN: 5136

South Asian (SAS) AF: 0.232 AC: 1117 AN: 4824

European-Finnish (FIN) AF: 0.341 AC: 3609 AN: 10580

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.354 AC: 24080 AN: 67960

Other (OTH) AF: 0.348 AC: 736 AN: 2116

Alfa AF: 0.356 Hom.: 21575

Bravo AF: 0.350

Asia WGS AF: 0.252 AC: 881 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.4
DANN	Benign	0.95
PhyloP100		-1.9
PromoterAI		-0.074	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=300/0	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: rs7242481; hg19: chr18-33709217;