Variant 5-175492132-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_022754.7(SFXN1):c.29A>G(p.Asn10Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,400 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SFXN1
NM_022754.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.20

Variant links:

Genes affected

SFXN1 (HGNC:16085): (sideroflexin 1) Enables D-serine transmembrane transporter activity and L-serine transmembrane transporter activity. Involved in D-serine transport; L-serine transport; and serine import into mitochondrion. Located in mitochondrion. Is integral component of mitochondrial inner membrane. [provided by Alliance of Genome Resources, Apr 2022]

SFXN1 links:

SFXN1 (HGNC:):

SFXN1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.35955247).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SFXN1	NM_022754.7 linkuse as main transcript	c.29A>G	p.Asn10Ser	missense_variant	2/11	ENST00000321442.10	NP_073591.2	Q9H9B4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SFXN1	ENST00000321442.10 linkuse as main transcript	c.29A>G	p.Asn10Ser	missense_variant	2/11	1	NM_022754.7	ENSP00000316905.5		Q9H9B4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461400

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726988

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:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

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

Ambry Genetics

Sep 24, 2024

The c.29A>G (p.N10S) alteration is located in exon 2 (coding exon 1) of the SFXN1 gene. This alteration results from a A to G substitution at nucleotide position 29, causing the asparagine (N) at amino acid position 10 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.066

T;T;T;T

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

D;D;D;D

M_CAP

Benign

0.019

MetaRNN

Benign

0.36

T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.8

.;L;.;.

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-3.0

D;D;.;D

REVEL

Benign

0.24

Sift

Uncertain

0.026

D;D;.;D

Sift4G

Uncertain

0.056

T;D;T;D

Polyphen

0.97

.;D;.;.

Vest4

0.63, 0.63

MutPred

0.32

Gain of glycosylation at N10 (P = 0.0318);Gain of glycosylation at N10 (P = 0.0318);Gain of glycosylation at N10 (P = 0.0318);Gain of glycosylation at N10 (P = 0.0318);

MVP

0.32

MPC

0.26

ClinPred

0.97

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.38

gMVP

0.70

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