17-5034118-G-A

Variant names:

• chr17-5034118-G-A
• rs146289149
• NM_017986.4:c.371C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_017986.4(SLC52A1):​c.371C>T​(p.Ala124Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000845 in 1,614,206 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A124T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0040 (7 hom., cov: 33)
  • Exomes 𝑓: 0.00051 (5 hom.)
• Consequence: SLC52A1 NM_017986.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.05
• Publications: 3 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: SUPPORTIVE, LIMITED Submitted by: ClinGen, Orphanet, Ambry Genetics
• ariboflavinosis

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

LOC105371501 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0039052963).
• BP6: Variant 17-5034118-G-A is Benign according to our data. Variant chr17-5034118-G-A is described in ClinVar as Benign. ClinVar VariationId is 377104.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAdExome4 allele frequency = 0.000513 (750/1461888) while in subpopulation AFR AF = 0.0162 (541/33480). AF 95% confidence interval is 0.015. There are 5 homozygotes in GnomAdExome4. There are 325 alleles in the male GnomAdExome4 subpopulation. Median coverage is 88. This position passed quality control check.
• BS2: High AC in GnomAd4 at 614 AD,Unknown gene.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC52A1	NM_017986.4	MANE Select	c.371C>T	p.Ala124Val	missense	Exon 3 of 5	NP_060456.3
	SLC52A1	NM_001104577.2		c.371C>T	p.Ala124Val	missense	Exon 3 of 5	NP_001098047.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC52A1	ENST00000254853.10	TSL:1 MANE Select	c.371C>T	p.Ala124Val	missense	Exon 3 of 5	ENSP00000254853.5
	SLC52A1	ENST00000424747.1	TSL:1	c.371C>T	p.Ala124Val	missense	Exon 3 of 5	ENSP00000399979.1
	SLC52A1	ENST00000512825.7	TSL:2	c.371C>T	p.Ala124Val	missense	Exon 3 of 4	ENSP00000443026.1

Frequencies

GnomAD3 genomes AF: 0.00398 AC: 605 AN: 152200 Hom.: 6 Cov.: 33

Gnomad AFR AF: 0.0135

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00121 AC: 305 AN: 251422 AF XY: 0.000817

Gnomad AFR exome AF: 0.0160

Gnomad AMR exome AF: 0.000520

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000167

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.000513 AC: 750 AN: 1461888 Hom.: 5 Cov.: 88 AF XY: 0.000447 AC XY: 325 AN XY: 727246

African (AFR) AF: 0.0162 AC: 541 AN: 33480

American (AMR) AF: 0.000492 AC: 22 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000104 AC: 9 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00208 AC: 12 AN: 5768

European-Non Finnish (NFE) AF: 0.0000773 AC: 86 AN: 1112010

Other (OTH) AF: 0.00132 AC: 80 AN: 60396

GnomAD4 genome AF: 0.00403 AC: 614 AN: 152318 Hom.: 7 Cov.: 33 AF XY: 0.00389 AC XY: 290 AN XY: 74484

African (AFR) AF: 0.0137 AC: 568 AN: 41572

American (AMR) AF: 0.00144 AC: 22 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68026

Other (OTH) AF: 0.00473 AC: 10 AN: 2114

Alfa AF: 0.00164 Hom.: 5

Bravo AF: 0.00490

ESP6500AA AF: 0.0154 AC: 68

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00140 AC: 170

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Jan 05, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Vitamin B2 deficiency Benign:1

Dec 04, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	18
DANN	Benign	0.14
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.76	T
MetaRNN	Benign	0.0039	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.040	N
PhyloP100		2.0
PrimateAI	Benign	0.27	T
PROVEAN	Benign	2.1	N
REVEL	Benign	0.14
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.061	B
Vest4		0.037
MVP		0.19
MPC		0.094
ClinPred		0.0064	T
GERP RS		1.8
Varity_R		0.050
gMVP		0.67
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs146289149; hg19: chr17-4937413;