5-151467755-A-G

Position:

• chr5-151467755-A-G

Variant summary

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

The NM_078483.4(SLC36A1):​c.553A>G​(p.Thr185Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: SLC36A1 NM_078483.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.31

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.553A>G	p.Thr185Ala	missense_variant	7/11	ENST00000243389.8	NP_510968.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC36A1	ENST00000243389.8	c.553A>G	p.Thr185Ala	missense_variant	7/11	1	NM_078483.4	ENSP00000243389.3
SLC36A1	ENST00000521925.5	c.553A>G	p.Thr185Ala	missense_variant	7/10	1		ENSP00000430305.1
SLC36A1	ENST00000429484.6	c.553A>G	p.Thr185Ala	missense_variant	7/9	1		ENSP00000395640.2
SLC36A1	ENST00000520701.5	c.553A>G	p.Thr185Ala	missense_variant	7/11	5		ENSP00000428140.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 30

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.553A>G (p.T185A) alteration is located in exon 7 (coding exon 6) of the SLC36A1 gene. This alteration results from a A to G substitution at nucleotide position 553, causing the threonine (T) at amino acid position 185 to be replaced by an alanine (A). 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	0.16
BayesDel_addAF	Benign	-0.0057	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.099	T;.;T;.;.
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.85	.;D;D;D;D
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.63	D;D;D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.8	M;M;M;M;.
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-2.5	D;N;D;.;D
REVEL	Benign	0.17
Sift	Benign	0.043	D;T;D;.;T
Sift4G	Benign	0.13	T;T;T;T;T
Polyphen		0.95	P;.;P;.;P
Vest4		0.65
MutPred		0.38		Gain of loop (P = 0.0851);Gain of loop (P = 0.0851);Gain of loop (P = 0.0851);Gain of loop (P = 0.0851);Gain of loop (P = 0.0851);
MVP		0.51
MPC		0.39
ClinPred		0.97	D
GERP RS		5.7
Varity_R		0.28
gMVP		0.72

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-150847316;