SLC29A3 p.Phe50Leu

Variant names:

• chr10-71322904-C-A
• NM_018344.6:c.150C>A
• SLC29A3 p.Phe50Leu

Your query was ambiguous. Multiple possible variants found:

• chr10-71322904-C-A
• chr10-71322904-C-G
• chr10-71322902-T-C
• chr10-71322902-TTC-CTT
• chr10-71322902-TTC-CTA
• chr10-71322902-TTC-CTG

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018344.6(SLC29A3):​c.150C>A​(p.Phe50Leu) 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. 13/22 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: SLC29A3 NM_018344.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.64
• Publications: 0 publications found

Genes affected

SLC29A3 (HGNC:23096): (solute carrier family 29 member 3) This gene encodes a nucleoside transporter. The encoded protein plays a role in cellular uptake of nucleosides, nucleobases, and their related analogs. Mutations in this gene have been associated with H syndrome, which is characterized by cutaneous hyperpigmentation and hypertrichosis, hepatosplenomegaly, heart anomalies, and hypogonadism. A related disorder, PHID (pigmented hypertrichosis with insulin-dependent diabetes mellitus), has also been associated with mutations at this locus. Alternatively spliced transcript variants have been described.[provided by RefSeq, Mar 2010]

SLC29A3 Gene-Disease associations (from GenCC):

• H syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), ClinGen, PanelApp Australia, Orphanet
• dysosteosclerosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13811064).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018344.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC29A3	NM_018344.6	MANE Select	c.150C>A	p.Phe50Leu	missense	Exon 2 of 6	NP_060814.4
	SLC29A3	NM_001363518.2		c.-85C>A		5_prime_UTR_premature_start_codon_gain	Exon 2 of 6	NP_001350447.1	A0A2R8YDR8
	SLC29A3	NM_001174098.2		c.150C>A	p.Phe50Leu	missense	Exon 2 of 6	NP_001167569.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC29A3	ENST00000373189.6	TSL:1 MANE Select	c.150C>A	p.Phe50Leu	missense	Exon 2 of 6	ENSP00000362285.5	Q9BZD2-1
	SLC29A3	ENST00000479577.2	TSL:2	c.-85C>A		5_prime_UTR_premature_start_codon_gain	Exon 2 of 6	ENSP00000493995.1	A0A2R8YDR8
	SLC29A3	ENST00000479577.2	TSL:2	c.-85C>A		5_prime_UTR	Exon 2 of 6	ENSP00000493995.1	A0A2R8YDR8

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Benign	-0.059	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	13
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	0.71	N
PhyloP100		1.6
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.11
Sift	Benign	0.099	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.16
gMVP		0.52

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr10-73082661;