4-42018125-A-G

Variant summary

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

The NM_006345.4(SLC30A9):c.289A>G(p.Thr97Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.976 in 1,554,576 control chromosomes in the GnomAD database, including 740,322 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.98 (72590 hom., cov: 31)
  • Exomes 𝑓: 0.98 (667732 hom.)
• Consequence: SLC30A9 NM_006345.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.484

Genes affected

SLC30A9 (HGNC:1329): (solute carrier family 30 member 9) Predicted to enable nuclear receptor coactivator activity. Involved in cellular zinc ion homeostasis and zinc ion transport. Located in several cellular components, including cytoplasmic vesicle; cytoskeleton; and endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=8.8965066E-7).
• BP6: Variant 4-42018125-A-G is Benign according to our data. Variant chr4-42018125-A-G is described in ClinVar as [Benign]. Clinvar id is 1333132.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC30A9	NM_006345.4	c.289A>G	p.Thr97Ala	missense_variant	3/18	ENST00000264451.12
SLC30A9	XM_047449525.1	c.289A>G	p.Thr97Ala	missense_variant	3/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC30A9	ENST00000264451.12	c.289A>G	p.Thr97Ala	missense_variant	3/18	1	NM_006345.4	P1
SLC30A9	ENST00000510460.1	n.414A>G		non_coding_transcript_exon_variant	3/4	2
SLC30A9	ENST00000513699.5	c.289A>G	p.Thr97Ala	missense_variant, NMD_transcript_variant	3/19	2

Frequencies

GnomAD3 genomes AF: 0.977 AC: 148500 AN: 152060 Hom.: 72529 Cov.: 31

Gnomad AFR AF: 0.973

Gnomad AMI AF: 0.964

Gnomad AMR AF: 0.987

Gnomad ASJ AF: 0.980

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.983

Gnomad FIN AF: 0.981

Gnomad MID AF: 0.991

Gnomad NFE AF: 0.974

Gnomad OTH AF: 0.977

GnomAD3 exomes AF: 0.980 AC: 242926 AN: 247992 Hom.: 118982 AF XY: 0.980 AC XY: 131456 AN XY: 134200

Gnomad AFR exome AF: 0.976

Gnomad AMR exome AF: 0.989

Gnomad ASJ exome AF: 0.981

Gnomad EAS exome AF: 0.996

Gnomad SAS exome AF: 0.981

Gnomad FIN exome AF: 0.977

Gnomad NFE exome AF: 0.975

Gnomad OTH exome AF: 0.979

GnomAD4 exome AF: 0.976 AC: 1368424 AN: 1402398 Hom.: 667732 Cov.: 23 AF XY: 0.976 AC XY: 683882 AN XY: 700832

Gnomad4 AFR exome AF: 0.977

Gnomad4 AMR exome AF: 0.989

Gnomad4 ASJ exome AF: 0.980

Gnomad4 EAS exome AF: 0.992

Gnomad4 SAS exome AF: 0.982

Gnomad4 FIN exome AF: 0.977

Gnomad4 NFE exome AF: 0.974

Gnomad4 OTH exome AF: 0.978

GnomAD4 genome AF: 0.977 AC: 148620 AN: 152178 Hom.: 72590 Cov.: 31 AF XY: 0.977 AC XY: 72665 AN XY: 74392

Gnomad4 AFR AF: 0.973

Gnomad4 AMR AF: 0.987

Gnomad4 ASJ AF: 0.980

Gnomad4 EAS AF: 0.995

Gnomad4 SAS AF: 0.983

Gnomad4 FIN AF: 0.981

Gnomad4 NFE AF: 0.974

Gnomad4 OTH AF: 0.976

Alfa AF: 0.976 Hom.: 142411

Bravo AF: 0.978

TwinsUK AF: 0.974 AC: 3613

ALSPAC AF: 0.973 AC: 3751

ESP6500AA AF: 0.975 AC: 4294

ESP6500EA AF: 0.976 AC: 8381

ExAC AF: 0.979 AC: 118853

Asia WGS AF: 0.986 AC: 3399 AN: 3446

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Psychomotor regression-oculomotor apraxia-movement disorder-nephropathy syndrome 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
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.80
Cadd	Benign	8.6
Dann	Benign	0.24
DEOGEN2	Benign	0.019	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.00060	N
LIST_S2	Benign	0.12	T
MetaRNN	Benign	8.9e-7	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.97	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.32	N
REVEL	Benign	0.14
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.033
MPC		0.42
ClinPred		0.000019	T
GERP RS		3.5
Varity_R		0.027
gMVP		0.13

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2581423; hg19: chr4-42020142;