rs547679833

Positions:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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).

• 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

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 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 id is 617856.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLVCR1	NM_014053.4	c.785A>C	p.Asn262Thr	missense_variant	2/10	ENST00000366971.9	NP_054772.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLVCR1	ENST00000366971.9	c.785A>C	p.Asn262Thr	missense_variant	2/10	1	NM_014053.4	ENSP00000355938	P1
FLVCR1	ENST00000419102.1	c.323A>C	p.Asn108Thr	missense_variant	2/9	5		ENSP00000414680
FLVCR1	ENST00000579295.1	n.141A>C		non_coding_transcript_exon_variant	1/3	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Short rib-polydactyly syndrome Pathogenic:1

Likely pathogenic, no assertion criteria provided

research

University of Washington Center for Mendelian Genomics, University of Washington

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Computational scores

Source: dbNSFP v4.3

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
MutationTaster	Benign	1.0	D
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

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: rs547679833; hg19: chr1-213037113;