chr13-28704313-T-C

Variant names:

• chr13-28704313-T-C
• rs1305088
• NM_181785.4:c.1145-214A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SLC46A3	NM_181785.4	c.1145-214A>G		intron_variant	Intron 4 of 5	ENST00000266943.11	NP_861450.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC46A3	ENST00000266943.11	c.1145-214A>G		intron_variant	Intron 4 of 5	1	NM_181785.4	ENSP00000266943.7
SLC46A3	ENST00000380814.4	c.1145-214A>G		intron_variant	Intron 4 of 6	1		ENSP00000370192.4
SLC46A3	ENST00000475385.1	n.245A>G		non_coding_transcript_exon_variant	Exon 1 of 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

African (AFR) AF: 0.701 AC: 7518 AN: 10724

American (AMR) AF: 0.911 AC: 12941 AN: 14208

Ashkenazi Jewish (ASJ) AF: 0.959 AC: 11490 AN: 11986

East Asian (EAS) AF: 0.685 AC: 18118 AN: 26440

South Asian (SAS) AF: 0.804 AC: 29247 AN: 36360

European-Finnish (FIN) AF: 0.954 AC: 22476 AN: 23570

Middle Eastern (MID) AF: 0.914 AC: 1565 AN: 1712

European-Non Finnish (NFE) AF: 0.942 AC: 221055 AN: 234684

Other (OTH) AF: 0.897 AC: 20108 AN: 22422

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

African (AFR) AF: 0.694 AC: 28770 AN: 41458

American (AMR) AF: 0.903 AC: 13811 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.963 AC: 3341 AN: 3470

East Asian (EAS) AF: 0.655 AC: 3390 AN: 5174

South Asian (SAS) AF: 0.781 AC: 3762 AN: 4818

European-Finnish (FIN) AF: 0.953 AC: 10104 AN: 10606

Middle Eastern (MID) AF: 0.918 AC: 270 AN: 294

European-Non Finnish (NFE) AF: 0.941 AC: 64002 AN: 68018

Other (OTH) AF: 0.886 AC: 1875 AN: 2116

Alfa AF: 0.912 Hom.: 297901

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
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1305088; hg19: chr13-29278450;