rs547679833

Variant names:

• chr1-212863771-A-C
• rs547679833
• NM_014053.4:c.785A>C

Your query was ambiguous. Multiple possible variants found:

• chr1-212863771-A-C
• chr1-212863771-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP5

The NM_014053.4(FLVCR1):​c.785A>C​(p.Asn262Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N262S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FLVCR1 NM_014053.4 missense
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.01
• Publications: 1 publications found

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: Labcorp Genetics (formerly Invitae), G2P, Orphanet, Illumina

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 1-212863771-A-C is Pathogenic according to our data. Variant chr1-212863771-A-C is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 617856.Status of the report is no_assertion_criteria_provided, 0 stars.

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.785A>C	p.Asn262Thr	missense	Exon 2 of 10	NP_054772.1	Q9Y5Y0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLVCR1	ENST00000366971.9	TSL:1 MANE Select	c.785A>C	p.Asn262Thr	missense	Exon 2 of 10	ENSP00000355938.4	Q9Y5Y0-1
	FLVCR1	ENST00000867613.1		c.785A>C	p.Asn262Thr	missense	Exon 2 of 11	ENSP00000537672.1
	FLVCR1	ENST00000971333.1		c.812A>C	p.Asn271Thr	missense	Exon 2 of 10	ENSP00000641392.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Short rib-polydactyly syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.023	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.52	D
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.0096	T
MetaRNN	Uncertain	0.56	D
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		5.0
PrimateAI	Uncertain	0.48	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Benign	0.28
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.025	D
Polyphen		0.92	P
Vest4		0.37
MutPred		0.58		Gain of glycosylation at N262 (P = 0.0123)
MVP		0.70
MPC		1.3
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.63
gMVP		0.41
Mutation Taster		=58/42	disease causing (ClinVar)

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: rs547679833; hg19: chr1-213037113;