Genetic Variant NM_181785.4:c.1145-214A>T (chr13-28704313-T-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_181785.4(SLC46A3):c.1145-214A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 30)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SLC46A3
NM_181785.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.94

Publications

13 publications found

Variant links:

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]

SLC46A3 links:

LOC124903143 (HGNC:):

LOC124903143 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC46A3	NM_181785.4 link	c.1145-214A>T		intron_variant	Intron 4 of 5	ENST00000266943.11	NP_861450.1	Q7Z3Q1-1A0A024RDN9

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC46A3	ENST00000266943.11 link	c.1145-214A>T	intron_variant	Intron 4 of 5	1	NM_181785.4	ENSP00000266943.7	Q7Z3Q1-1
SLC46A3	ENST00000380814.4 link	c.1145-214A>T	intron_variant	Intron 4 of 6	1		ENSP00000370192.4	Q7Z3Q1-2
SLC46A3	ENST00000475385.1 link	n.245A>T	non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

382374

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

201608

African (AFR)

AF:

0.00

AC:

AN:

10736

American (AMR)

AF:

0.00

AC:

AN:

14224

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11988

East Asian (EAS)

AF:

0.00

AC:

AN:

26492

South Asian (SAS)

AF:

0.00

AC:

AN:

36396

European-Finnish (FIN)

AF:

0.00

AC:

AN:

23582

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1712

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

234796

Other (OTH)

AF:

0.00

AC:

AN:

22448

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.14

(source)

DANN

Benign

0.61

PhyloP100

-1.9

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over