5-151277505-A-G

Position:

• chr5-151277505-A-G

Variant summary

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

The NM_181774.4(SLC36A3):​c.1301T>C​(p.Met434Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 0.0000034 (0 hom.)
• Consequence: SLC36A3 NM_181774.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.88

Genes affected

SLC36A3 (HGNC:19659): (solute carrier family 36 member 3) Predicted to enable amino acid transmembrane transporter activity. Predicted to be involved in amino acid transport and proton transmembrane transport. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.13971692).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC36A3	NM_181774.4	c.1301T>C	p.Met434Thr	missense_variant	10/10	ENST00000335230.8	NP_861439.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC36A3	ENST00000335230.8	c.1301T>C	p.Met434Thr	missense_variant	10/10	1	NM_181774.4	ENSP00000334750	P1
SLC36A3	ENST00000377713.3	c.1424T>C	p.Met475Thr	missense_variant	11/11	1		ENSP00000366942
SLC36A3	ENST00000423071.2	n.3201T>C		non_coding_transcript_exon_variant	9/9	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461892 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727248

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: 0.0000580

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

Dec 01, 2022

The c.1424T>C (p.M475T) alteration is located in exon 11 (coding exon 11) of the SLC36A3 gene. This alteration results from a T to C substitution at nucleotide position 1424, causing the methionine (M) at amino acid position 475 to be replaced by a threonine (T). 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	0.10
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0065	T;.
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.0063
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.68	T;T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	0.63	N;.
MutationTaster	Benign	0.90	D;D
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.5	N;N
REVEL	Benign	0.045
Sift	Benign	0.079	T;T
Sift4G	Benign	0.16	T;T
Polyphen		0.0040	B;B
Vest4		0.14
MutPred		0.62		Loss of stability (P = 0.0151);.;
MVP		0.24
MPC		0.038
ClinPred		0.62	D
GERP RS		4.5
Varity_R		0.21
gMVP		0.44

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: chr5-150657066;