dbSNP rs41296694: FLVCR1:p.Leu199Val (chr1-212859047-C-G) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 4P and 1B. PM2PM5BP4

The NM_014053.4(FLVCR1):c.595C>G(p.Leu199Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. L199F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

FLVCR1
NM_014053.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.69

Publications

4 publications found

Variant links:

Genes affected

FLVCR1 (HGNC:24682): (FLVCR choline and heme transporter 1) This gene encodes a member of the major facilitator superfamily of transporter proteins. The encoded protein is a heme transporter that may play a critical role in erythropoiesis by protecting developing erythroid cells from heme toxicity. This gene may play a role in posterior column ataxia with retinitis pigmentosa and the hematological disorder Diamond-Blackfan syndrome. [provided by RefSeq, Jan 2011]

FLVCR1 Gene-Disease associations (from GenCC):

FLVCR1-related retinopathy with or without ataxia
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
posterior column ataxia-retinitis pigmentosa syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Illumina, Labcorp Genetics (formerly Invitae), G2P, Orphanet

FLVCR1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM5

Other missense variant is known to change same aminoacid residue: Variant chr1-212859048-T-C is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 3767315.Status of the report is criteria_provided_single_submitter, 1 stars.

BP4

Computational evidence support a benign effect (MetaRNN=0.38469583).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014053.4. 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
	FLVCR1	NM_014053.4	MANE Select	c.595C>G	p.Leu199Val	missense	Exon 1 of 10	NP_054772.1	Q9Y5Y0-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FLVCR1	ENST00000366971.9	TSL:1 MANE Select	c.595C>G	p.Leu199Val	missense	Exon 1 of 10	ENSP00000355938.4	Q9Y5Y0-1
FLVCR1	ENST00000867613.1		c.595C>G	p.Leu199Val	missense	Exon 1 of 11	ENSP00000537672.1
FLVCR1	ENST00000971333.1		c.595C>G	p.Leu199Val	missense	Exon 1 of 10	ENSP00000641392.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000400

AC:

AN:

250250

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

0.0036

BayesDel_noAF

Uncertain

-0.060

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.34

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.90

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.38

MetaSVM

Uncertain

0.67

MutationAssessor

Uncertain

2.8

PhyloP100

5.7

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-2.4

REVEL

Uncertain

0.59

Sift

Benign

0.053

Sift4G

Uncertain

0.056

Polyphen

0.76

Vest4

0.34

MutPred

0.60

Gain of helix (P = 0.1736)

MVP

0.99

MPC

1.6

ClinPred

0.97

GERP RS

5.4

PromoterAI

0.017

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.55

gMVP

0.23

Mutation Taster

=64/36

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over