1-205659459-C-G

Position:

• chr1-205659459-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_033102.3(SLC45A3):​c.1437G>C​(p.Glu479Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E479K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC45A3 NM_033102.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.175

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]

SLC45A3 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06270957).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC45A3	NM_033102.3	c.1437G>C	p.Glu479Asp	missense_variant	5/5	ENST00000367145.4	NP_149093.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC45A3	ENST00000367145.4	c.1437G>C	p.Glu479Asp	missense_variant	5/5	1	NM_033102.3	ENSP00000356113.3
SLC45A3	ENST00000460934.1	n.840G>C		non_coding_transcript_exon_variant	3/3	1

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

Jul 26, 2024

The c.1437G>C (p.E479D) alteration is located in exon 5 (coding exon 4) of the SLC45A3 gene. This alteration results from a G to C substitution at nucleotide position 1437, causing the glutamic acid (E) at amino acid position 479 to be replaced by an aspartic acid (D). 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	0.075
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	9.1
DANN	Uncertain	0.99
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.26	N
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	-0.40	N
REVEL	Benign	0.075
Sift	Benign	0.18	T
Sift4G	Benign	0.43	T
Polyphen		0.0	B
Vest4		0.027
MutPred		0.29		Loss of sheet (P = 0.0104);
MVP		0.048
MPC		0.32
ClinPred		0.17	T
GERP RS		3.5
Varity_R		0.051
gMVP		0.63

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: chr1-205628587; COSMIC: COSV99056858;