5-151464526-A-T

Position:

• chr5-151464526-A-T

Variant summary

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

The NM_078483.4(SLC36A1):​c.247A>T​(p.Ser83Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC36A1 NM_078483.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.73

Genes affected

SLC36A1 (HGNC:18761): (solute carrier family 36 member 1) This gene encodes a member of the eukaryote-specific amino acid/auxin permease (AAAP) 1 transporter family. The encoded protein functions as a proton-dependent, small amino acid transporter. This gene is clustered with related family members on chromosome 5q33.1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

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
SLC36A1	NM_078483.4	c.247A>T	p.Ser83Cys	missense_variant	4/11	ENST00000243389.8	NP_510968.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC36A1	ENST00000243389.8	c.247A>T	p.Ser83Cys	missense_variant	4/11	1	NM_078483.4	ENSP00000243389.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Aug 01, 2024

The c.247A>T (p.S83C) alteration is located in exon 4 (coding exon 3) of the SLC36A1 gene. This alteration results from a A to T substitution at nucleotide position 247, causing the serine (S) at amino acid position 83 to be replaced by a cysteine (C). 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	Benign	-0.054	T
BayesDel_noAF	Benign	-0.32
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	.;T;.;T;.;.
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.85	D;.;D;D;D;D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.53	D;D;D;D;D;D
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.3	.;M;M;M;M;.
PrimateAI	Uncertain	0.58	T
PROVEAN	Pathogenic	-4.8	D;D;D;D;.;D
REVEL	Benign	0.27
Sift	Pathogenic	0.0	D;D;D;D;.;D
Sift4G	Benign	0.069	T;T;T;T;T;T
Polyphen		1.0, 0.76	.;D;.;D;.;P
Vest4		0.51, 0.51, 0.51, 0.51
MutPred		0.63		Loss of glycosylation at S83 (P = 0.0615);Loss of glycosylation at S83 (P = 0.0615);Loss of glycosylation at S83 (P = 0.0615);Loss of glycosylation at S83 (P = 0.0615);Loss of glycosylation at S83 (P = 0.0615);Loss of glycosylation at S83 (P = 0.0615);
MVP		0.41
MPC		0.77
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.55
gMVP		0.70

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-150844087;