chr11-57415095-C-A

Variant names:

• chr11-57415095-C-A
• rs768402677
• NM_199329.3:c.781G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_199329.3(SLC43A3):​c.781G>T​(p.Ala261Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000597 in 1,457,210 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: 0.000060 (0 hom.)
• Consequence: SLC43A3 NM_199329.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.328

Genes affected

SLC43A3 (HGNC:17466): (solute carrier family 43 member 3) Predicted to enable transmembrane transporter activity. Predicted to be involved in transmembrane transport. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000254979 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0096443).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC43A3	NM_199329.3	c.781G>T	p.Ala261Ser	missense_variant	Exon 10 of 14	ENST00000395124.6	NP_955361.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC43A3	ENST00000395124.6	c.781G>T	p.Ala261Ser	missense_variant	Exon 10 of 14	1	NM_199329.3	ENSP00000378556.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.000147 AC: 36 AN: 245720 Hom.: 0 AF XY: 0.000136 AC XY: 18 AN XY: 132522

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00122

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000597 AC: 87 AN: 1457210 Hom.: 0 Cov.: 32 AF XY: 0.0000745 AC XY: 54 AN XY: 724578

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000902

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.000166

GnomAD4 genome Cov.: 32

ExAC AF: 0.000173 AC: 21

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 01, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.781G>T (p.A261S) alteration is located in exon 10 (coding exon 8) of the SLC43A3 gene. This alteration results from a G to T substitution at nucleotide position 781, causing the alanine (A) at amino acid position 261 to be replaced by a serine (S). 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	0.070
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	1.3
DANN	Benign	0.47
DEOGEN2	Benign	0.13	T;T;T;T;.;T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.074	N
LIST_S2	Benign	0.59	.;.;.;T;T;T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.0096	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L;L;L;L;.;.
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.53	N;N;N;N;N;N
REVEL	Benign	0.018
Sift	Benign	0.50	T;T;T;T;T;T
Sift4G	Benign	0.64	T;T;T;T;T;.
Polyphen		0.0010	B;B;B;B;.;.
Vest4		0.036
MutPred		0.30		Gain of glycosylation at A261 (P = 0.0082);Gain of glycosylation at A261 (P = 0.0082);Gain of glycosylation at A261 (P = 0.0082);Gain of glycosylation at A261 (P = 0.0082);.;Gain of glycosylation at A261 (P = 0.0082);
MVP		0.12
MPC		0.10
ClinPred		0.019	T
GERP RS		-2.3
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.0
Varity_R		0.080
gMVP		0.24

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs768402677; hg19: chr11-57182568;