3-126012728-G-C

Position:

• chr3-126012728-G-C

Variant summary

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

The NM_017836.4(SLC41A3):​c.992C>G​(p.Ala331Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLC41A3 NM_017836.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.18

Genes affected

SLC41A3 (HGNC:31046): (solute carrier family 41 member 3) Predicted to enable cation transmembrane transporter activity. Predicted to be involved in cation transmembrane transport. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC41A3 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC41A3	NM_017836.4	c.992C>G	p.Ala331Gly	missense_variant	9/11	ENST00000360370.9	NP_060306.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC41A3	ENST00000360370.9	c.992C>G	p.Ala331Gly	missense_variant	9/11	1	NM_017836.4	ENSP00000353533.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461882 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727238

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 20, 2024

The c.992C>G (p.A331G) alteration is located in exon 9 (coding exon 8) of the SLC41A3 gene. This alteration results from a C to G substitution at nucleotide position 992, causing the alanine (A) at amino acid position 331 to be replaced by a glycine (G). 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	0.25
BayesDel_addAF	Uncertain	0.086	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	.;.;.;T;.
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.95	D;D;D;D;D
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.66	D;D;D;D;D
MetaSVM	Benign	-0.79	T
MutationAssessor	Pathogenic	3.1	M;.;.;M;.
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-3.5	D;D;D;D;D
REVEL	Benign	0.23
Sift	Uncertain	0.0070	D;D;D;D;D
Sift4G	Uncertain	0.056	T;D;T;T;T
Polyphen		1.0, 0.99	.;D;D;D;.
Vest4		0.66
MutPred		0.60		Loss of glycosylation at S335 (P = 0.0605);.;.;Loss of glycosylation at S335 (P = 0.0605);.;
MVP		0.52
MPC		0.63
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.50
gMVP		0.70

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: chr3-125731571;