17-73031561-G-C

Variant summary

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

The NM_139177.4(SLC39A11):c.301C>G(p.His101Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: SLC39A11 NM_139177.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0890

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=0.08953935).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC39A11	NM_139177.4	c.301C>G	p.His101Asp	missense_variant	4/10	ENST00000255559.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC39A11	ENST00000255559.8	c.301C>G	p.His101Asp	missense_variant	4/10	1	NM_139177.4	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 31, 2023

The c.301C>G (p.H101D) alteration is located in exon 4 (coding exon 3) of the SLC39A11 gene. This alteration results from a C to G substitution at nucleotide position 301, causing the histidine (H) at amino acid position 101 to be replaced by an aspartic acid (D). 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	0.12
BayesDel_addAF	Benign	-0.065	T
BayesDel_noAF	Benign	-0.33
Cadd	Benign	15
Dann	Benign	0.95
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.18	N
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.090	T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	2.0	M;M;.;.;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-2.1	N;N;.;.;.
REVEL	Benign	0.16
Sift	Benign	0.14	T;T;.;.;.
Sift4G	Benign	0.086	T;T;T;.;.
Polyphen		0.015	B;B;.;.;.
Vest4		0.40
MutPred		0.57		Gain of disorder (P = 0.1413);Gain of disorder (P = 0.1413);Gain of disorder (P = 0.1413);Gain of disorder (P = 0.1413);Gain of disorder (P = 0.1413);
MVP		0.21
MPC		0.20
ClinPred		0.073	T
GERP RS		0.64
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.072
gMVP		0.63

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-71027700;