rs148979394

chr17-5032983-C-Gchr17-5032983-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_017986.4(SLC52A1):c.1321G>C(p.Asp441His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000929 in 1,613,774 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00064 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00096 (1 hom.)
• Consequence: SLC52A1 NM_017986.4 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.693

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]

LOC105371501 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.015421689).
• BP6: Variant 17-5032983-C-G is Benign according to our data. Variant chr17-5032983-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 574646.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd at 98 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC52A1	NM_017986.4	c.1321G>C	p.Asp441His	missense_variant	5/5	ENST00000254853.10
LOC105371501	XR_002958101.2	n.339+1314C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC52A1	ENST00000254853.10	c.1321G>C	p.Asp441His	missense_variant	5/5	1	NM_017986.4	P1

Frequencies

GnomAD3 genomes AF: 0.000644 AC: 98 AN: 152150 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000985

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.000739 AC: 185 AN: 250430 Hom.: 0 AF XY: 0.000783 AC XY: 106 AN XY: 135332

Gnomad AFR exome AF: 0.000370

Gnomad AMR exome AF: 0.000434

Gnomad ASJ exome AF: 0.00318

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.000282

Gnomad NFE exome AF: 0.000989

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.000959 AC: 1401 AN: 1461506 Hom.: 1 Cov.: 30 AF XY: 0.000905 AC XY: 658 AN XY: 727008

Gnomad4 AFR exome AF: 0.0000896

Gnomad4 AMR exome AF: 0.000470

Gnomad4 ASJ exome AF: 0.00314

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000116

Gnomad4 FIN exome AF: 0.000264

Gnomad4 NFE exome AF: 0.00107

Gnomad4 OTH exome AF: 0.00111

GnomAD4 genome AF: 0.000644 AC: 98 AN: 152268 Hom.: 0 Cov.: 31 AF XY: 0.000699 AC XY: 52 AN XY: 74444

Gnomad4 AFR AF: 0.000193

Gnomad4 AMR AF: 0.000523

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.000985

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00124 Hom.: 0

Bravo AF: 0.000646

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00105 AC: 9

ExAC AF: 0.000832 AC: 101

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00185

EpiControl AF: 0.00172

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

SLC52A1-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 02, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Ariboflavinosis Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 11, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.32
Cadd	Benign	19
Dann	Benign	0.83
DEOGEN2	Benign	0.059	T;T
Eigen	Benign	-0.055
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.72	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.015	T;T
MetaSVM	Benign	-0.39	T
MutationAssessor	Uncertain	2.6	M;M
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.2	N;N
REVEL	Uncertain	0.31
Sift	Benign	0.53	T;T
Sift4G	Benign	0.54	T;T
Polyphen		1.0	D;D
Vest4		0.22
MVP		0.41
MPC		0.49
ClinPred		0.029	T
GERP RS		0.91
Varity_R		0.10
gMVP		0.35

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

LitVar

Other links and lift over

dbSNP: rs148979394; hg19: chr17-4936278;