1-205663031-C-A

Position:

• chr1-205663031-C-A

Variant summary

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

The NM_033102.3(SLC45A3):​c.760G>T​(p.Gly254Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 33)
• Consequence: SLC45A3 NM_033102.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.75

Genes affected

SLC45A3 (HGNC:8642): (solute carrier family 45 member 3) Predicted to enable sucrose:proton symporter activity. Predicted to be involved in positive regulation of small molecule metabolic process; regulation of oligodendrocyte differentiation; and sucrose transport. Predicted to be located in plasma membrane. Predicted to be active in 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=0.14627337).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC45A3	NM_033102.3	c.760G>T	p.Gly254Cys	missense_variant	3/5	ENST00000367145.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC45A3	ENST00000367145.4	c.760G>T	p.Gly254Cys	missense_variant	3/5	1	NM_033102.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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

Nov 18, 2022

The c.760G>T (p.G254C) alteration is located in exon 3 (coding exon 2) of the SLC45A3 gene. This alteration results from a G to T substitution at nucleotide position 760, causing the glycine (G) at amino acid position 254 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	0.11
BayesDel_addAF	Benign	-0.075	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.69	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.61	T
MutationAssessor	Benign	-0.95	N
MutationTaster	Benign	0.84	D
PrimateAI	Benign	0.45	T
PROVEAN	Benign	0.45	N
REVEL	Benign	0.14
Sift	Benign	0.20	T
Sift4G	Benign	0.18	T
Polyphen		0.0	B
Vest4		0.085
MutPred		0.50		Loss of MoRF binding (P = 0.0818);
MVP		0.77
MPC		0.38
ClinPred		0.73	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
gMVP		0.39

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: chr1-205632159;