1-205659671-C-T

Position:

• chr1-205659671-C-T

Variant summary

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

The NM_033102.3(SLC45A3):​c.1225G>A​(p.Val409Met) variant causes a missense, splice region 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. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC45A3 NM_033102.3 missense, splice_region
• Scores: Splicing: ADA: 0.9994
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.57

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC45A3	NM_033102.3	c.1225G>A	p.Val409Met	missense_variant, splice_region_variant	5/5	ENST00000367145.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC45A3	ENST00000367145.4	c.1225G>A	p.Val409Met	missense_variant, splice_region_variant	5/5	1	NM_033102.3	P1
SLC45A3	ENST00000460934.1	n.628G>A		splice_region_variant, 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

Feb 07, 2023

The c.1225G>A (p.V409M) alteration is located in exon 5 (coding exon 4) of the SLC45A3 gene. This alteration results from a G to A substitution at nucleotide position 1225, causing the valine (V) at amino acid position 409 to be replaced by a methionine (M). 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	0.44
BayesDel_addAF	Benign	-0.046	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.032	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.1	M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.12
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.98	D
Vest4		0.37
MutPred		0.30		Gain of disorder (P = 0.0581);
MVP		0.48
MPC		0.87
ClinPred		0.92	D
GERP RS		5.3
Varity_R		0.17
gMVP		0.68

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.87
SpliceAI score (max)		0.10		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: chr1-205628799;