Variant rs754192985 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_StrongPM2

The NM_213649.2(SFXN4):c.32del(p.Pro11LeufsTer5) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000527 in 1,592,764 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000053 ( 0 hom. )

Consequence

SFXN4
NM_213649.2 frameshift

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.592

Variant links:

Genes affected

SFXN4 (HGNC:16088): (sideroflexin 4) This gene encodes a member of the sideroflexin family. The encoded protein is a transmembrane protein of the inner mitochondrial membrane, and is required for mitochondrial respiratory homeostasis and erythropoiesis. Mutations in this gene are associated with mitochondriopathy and macrocytic anemia. Alternatively spliced transcript variants have been found in this gene. [provided by RefSeq, Jan 2014]

SFXN4 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 5 pathogenic variants in the truncated region.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SFXN4	NM_213649.2 linkuse as main transcript	c.32del	p.Pro11LeufsTer5	frameshift_variant	1/14	ENST00000355697.7
SFXN4	XM_005269525.6 linkuse as main transcript	c.32del	p.Pro11LeufsTer5	frameshift_variant	1/13
SFXN4	XM_047424584.1 linkuse as main transcript	c.32del	p.Pro11LeufsTer5	frameshift_variant	1/14
SFXN4	NR_110305.1 linkuse as main transcript	n.77del		non_coding_transcript_exon_variant	1/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SFXN4	ENST00000355697.7 linkuse as main transcript	c.32del	p.Pro11LeufsTer5	frameshift_variant	1/14	1	NM_213649.2	P1	Q6P4A7-1
SFXN4	ENST00000461438.5 linkuse as main transcript	n.39del		non_coding_transcript_exon_variant	1/15	5
SFXN4	ENST00000466218.5 linkuse as main transcript	n.8del		non_coding_transcript_exon_variant	1/11	5

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152030

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000883

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000941

AC:

AN:

223178

Hom.:

AF XY:

0.0000815

AC XY:

AN XY:

122740

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000587

Gnomad NFE exome

AF:

0.0000705

Gnomad OTH exome

AF:

0.000374

GnomAD4 exome

AF:

0.0000534

AC:

AN:

1440734

Hom.:

Cov.:

AF XY:

0.0000586

AC XY:

AN XY:

717142

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00111

Gnomad4 NFE exome

AF:

0.0000163

Gnomad4 OTH exome

AF:

0.0000336

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152030

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74270

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000944

Gnomad4 NFE

AF:

0.0000883

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000182

Hom.:

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Nov 23, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over