17-72947746-C-T

Variant names:

• chr17-72947746-C-T
• NM_139177.4:c.430+6G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001159770.2(SLC39A11):​c.436G>A​(p.Ala146Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,550 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLC39A11 NM_001159770.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.315

Genes affected

SLC39A11 (HGNC:14463): (solute carrier family 39 member 11) Predicted to enable zinc ion transmembrane transporter activity. Predicted to be involved in zinc ion transmembrane transport. Predicted to be located in Golgi apparatus; nucleus; and plasma membrane. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12301192).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC39A11	NM_139177.4	c.430+6G>A		splice_region_variant, intron_variant	Intron 5 of 9	ENST00000255559.8	NP_631916.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC39A11	ENST00000255559.8	c.430+6G>A		splice_region_variant, intron_variant	Intron 5 of 9	1	NM_139177.4	ENSP00000255559.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461550 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 727074

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 28, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.436G>A (p.A146T) alteration is located in exon 5 (coding exon 4) of the SLC39A11 gene. This alteration results from a G to A substitution at nucleotide position 436, causing the alanine (A) at amino acid position 146 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	16
DANN	Benign	0.87
DEOGEN2	Benign	0.0020	T;.;.
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.24	N
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	0.81	L;.;.
PrimateAI	Benign	0.37	T
PROVEAN	Benign	0.19	N;.;.
REVEL	Benign	0.23
Sift	Benign	0.49	T;.;.
Sift4G	Benign	0.41	T;.;.
Polyphen		0.0	B;.;.
Vest4		0.068
MutPred		0.37		Gain of sheet (P = 0.0344);.;Gain of sheet (P = 0.0344);
MVP		0.54
MPC		0.14
ClinPred		0.093	T
GERP RS		1.0
Varity_R		0.030
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-70943885;