11-93148700-A-T

Variant summary

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

The NM_152313.4(SLC36A4):c.1352T>A(p.Leu451Gln) 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: SLC36A4 NM_152313.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.62

Genes affected

SLC36A4 (HGNC:19660): (solute carrier family 36 member 4) SLC36A4 belongs to the SLC36 family of amino acid transporters based on sequence similarity with other family members (e.g., SLC36A1; MIM 606561). SLC36 proteins contain about 500 amino acids and have 9 to 11 transmembrane domains. Unlike other SLC36 family members, which are proton-coupled amino acid transporters, SLC36A4 is a high-affinity/low-capacity non-proton-coupled amino acid transporter (Pillai and Meredith, 2011 [PubMed 21097500]).[supplied by OMIM, Feb 2011]

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	UniProt
SLC36A4	NM_152313.4	c.1352T>A	p.Leu451Gln	missense_variant	11/11	ENST00000326402.9
SLC36A4	NM_001286139.2	c.947T>A	p.Leu316Gln	missense_variant	11/11
SLC36A4	XM_047426350.1	c.1295T>A	p.Leu432Gln	missense_variant	11/11
SLC36A4	XM_047426351.1	c.1034T>A	p.Leu345Gln	missense_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC36A4	ENST00000326402.9	c.1352T>A	p.Leu451Gln	missense_variant	11/11	1	NM_152313.4	P1
SLC36A4	ENST00000529184.5	c.947T>A	p.Leu316Gln	missense_variant	11/11	2
SLC36A4	ENST00000527503.1	n.1526T>A		non_coding_transcript_exon_variant	2/2	2

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

Oct 05, 2023

The c.1352T>A (p.L451Q) alteration is located in exon 11 (coding exon 11) of the SLC36A4 gene. This alteration results from a T to A substitution at nucleotide position 1352, causing the leucine (L) at amino acid position 451 to be replaced by a glutamine (Q). 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	Uncertain	0.56
BayesDel_addAF	Uncertain	0.056	T
BayesDel_noAF	Benign	-0.16
Cadd	Uncertain	24
Dann	Uncertain	0.99
DEOGEN2	Benign	0.069	T;.
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.83	T;T
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.51	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M;.
MutationTaster	Benign	0.79	D;D
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-2.6	D;D
REVEL	Benign	0.19
Sift	Benign	0.036	D;D
Sift4G	Uncertain	0.035	D;T
Polyphen		0.96	D;.
Vest4		0.70
MutPred		0.36		Loss of stability (P = 0.0473);.;
MVP		0.28
MPC		0.24
ClinPred		0.97	D
GERP RS		5.5
Varity_R		0.66
gMVP		0.62

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: chr11-92881866;