chr5-151476680-A-T

Position:

• chr5-151476680-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_078483.4(SLC36A1):​c.913A>T​(p.Ser305Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000684 in 1,461,524 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000068 (1 hom.)
• Consequence: SLC36A1 NM_078483.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.43

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19231173).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC36A1	NM_078483.4	c.913A>T	p.Ser305Cys	missense_variant	9/11	ENST00000243389.8	NP_510968.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC36A1	ENST00000243389.8	c.913A>T	p.Ser305Cys	missense_variant	9/11	1	NM_078483.4	ENSP00000243389.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461524 Hom.: 1 Cov.: 31 AF XY: 0.0000110 AC XY: 8 AN XY: 727048

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.0000166

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

Feb 28, 2024

The c.913A>T (p.S305C) alteration is located in exon 9 (coding exon 8) of the SLC36A1 gene. This alteration results from a A to T substitution at nucleotide position 913, causing the serine (S) at amino acid position 305 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	0.011	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	22
DANN	Benign	0.85
DEOGEN2	Benign	0.10	T;T;.;.;.
Eigen	Benign	-0.0013
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.62	.;T;T;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.19	T;T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.81	L;L;L;.;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.9	N;N;.;N;N
REVEL	Benign	0.15
Sift	Benign	0.24	T;T;.;T;T
Sift4G	Benign	0.19	T;T;T;T;T
Polyphen		0.0060	B;B;.;B;.
Vest4		0.80
MutPred		0.43		Loss of stability (P = 0.1526);Loss of stability (P = 0.1526);Loss of stability (P = 0.1526);Loss of stability (P = 0.1526);.;
MVP		0.30
MPC		0.29
ClinPred		0.68	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.43
gMVP		0.67

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

LitVar

Other links and lift over

dbSNP: rs868368861; hg19: chr5-150856241;