17-5033861-C-A

Variant names:

• chr17-5033861-C-A
• rs139373407
• NM_017986.4:c.628G>T

Variant summary

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

The NM_017986.4(SLC52A1):​c.628G>T​(p.Ala210Ser) 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. 14/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. A210T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC52A1 NM_017986.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.252
• Publications: 2 publications found

Genes affected

SLC52A1 (HGNC:30225): (solute carrier family 52 member 1) Biological redox reactions require electron donors and acceptor. Vitamin B2 is the source for the flavin in flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) which are common redox reagents. This gene encodes a member of the riboflavin (vitamin B2) transporter family. Haploinsufficiency of this protein can cause maternal riboflavin deficiency. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jan 2013]

SLC52A1 Gene-Disease associations (from GenCC):

• maternal riboflavin deficiency

  Inheritance: AD Classification: MODERATE, SUPPORTIVE, LIMITED Submitted by: ClinGen, Orphanet, Ambry Genetics
• ariboflavinosis

  Inheritance: Unknown, AD Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia

LOC105371501 (HGNC:):

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=0.17867476).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017986.4. 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
	SLC52A1	NM_017986.4	MANE Select	c.628G>T	p.Ala210Ser	missense	Exon 3 of 5	NP_060456.3
	SLC52A1	NM_001104577.2		c.628G>T	p.Ala210Ser	missense	Exon 3 of 5	NP_001098047.1	Q9NWF4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC52A1	ENST00000254853.10	TSL:1 MANE Select	c.628G>T	p.Ala210Ser	missense	Exon 3 of 5	ENSP00000254853.5	Q9NWF4-1
	SLC52A1	ENST00000424747.1	TSL:1	c.628G>T	p.Ala210Ser	missense	Exon 3 of 5	ENSP00000399979.1	Q9NWF4-1
	SLC52A1	ENST00000894338.1		c.628G>T	p.Ala210Ser	missense	Exon 3 of 5	ENSP00000564397.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 89

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.053	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.040	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.047	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.50	T
MutationAssessor	Benign	2.0	M
PhyloP100		-0.25
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.34
Sift	Benign	0.17	T
Sift4G	Benign	0.15	T
Polyphen		0.96	D
Vest4		0.16
MutPred		0.52		Gain of phosphorylation at A210 (P = 0.069)
MVP		0.31
MPC		0.25
ClinPred		0.79	D
GERP RS		1.1
Varity_R		0.10
gMVP		0.46

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

Other links and lift over

dbSNP: rs139373407; hg19: chr17-4937156;