13-28704313-T-C

Position:

• chr13-28704313-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181785.4(SLC46A3):​c.1145-214A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.889 in 534,266 control chromosomes in the GnomAD database, including 213,474 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.86 (56755 hom., cov: 30)
  • Exomes 𝑓: 0.90 (156719 hom.)
• Consequence: SLC46A3 NM_181785.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94

Genes affected

SLC46A3 (HGNC:27501): (solute carrier family 46 member 3) The protein encoded by this gene is a member of a transmembrane protein family that transports small molecules across membranes. The encoded protein has been found in lysosomal membranes, where it can transport catabolites from the lysosomes to the cytoplasm. This protein has been shown to be an effective transporter of the cytotoxic drug maytansine, which is used in antibody-based targeting of cancer cells. [provided by RefSeq, Dec 2016]

LOC124903143 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC46A3	NM_181785.4	c.1145-214A>G		intron_variant		ENST00000266943.11
LOC124903143	XR_007063738.1	n.410-118T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC46A3	ENST00000266943.11	c.1145-214A>G		intron_variant		1	NM_181785.4	P1
SLC46A3	ENST00000380814.4	c.1145-214A>G		intron_variant		1
SLC46A3	ENST00000475385.1	n.245A>G		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes AF: 0.856 AC: 130155 AN: 152042 Hom.: 56732 Cov.: 30

Gnomad AFR AF: 0.694

Gnomad AMI AF: 0.988

Gnomad AMR AF: 0.903

Gnomad ASJ AF: 0.963

Gnomad EAS AF: 0.656

Gnomad SAS AF: 0.780

Gnomad FIN AF: 0.953

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.941

Gnomad OTH AF: 0.887

GnomAD4 exome AF: 0.902 AC: 344518 AN: 382106 Hom.: 156719 Cov.: 4 AF XY: 0.898 AC XY: 180839 AN XY: 201470

Gnomad4 AFR exome AF: 0.701

Gnomad4 AMR exome AF: 0.911

Gnomad4 ASJ exome AF: 0.959

Gnomad4 EAS exome AF: 0.685

Gnomad4 SAS exome AF: 0.804

Gnomad4 FIN exome AF: 0.954

Gnomad4 NFE exome AF: 0.942

Gnomad4 OTH exome AF: 0.897

GnomAD4 genome AF: 0.856 AC: 130224 AN: 152160 Hom.: 56755 Cov.: 30 AF XY: 0.856 AC XY: 63700 AN XY: 74412

Gnomad4 AFR AF: 0.694

Gnomad4 AMR AF: 0.903

Gnomad4 ASJ AF: 0.963

Gnomad4 EAS AF: 0.655

Gnomad4 SAS AF: 0.781

Gnomad4 FIN AF: 0.953

Gnomad4 NFE AF: 0.941

Gnomad4 OTH AF: 0.886

Alfa AF: 0.924 Hom.: 151879

Bravo AF: 0.846

Asia WGS AF: 0.684 AC: 2381 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.16
DANN	Benign	0.63

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: rs1305088; hg19: chr13-29278450;