5-175492180-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_022754.7(SFXN1):ā€‹c.77A>Gā€‹(p.Asn26Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 1,614,124 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā˜…). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: š‘“ 0.0053 ( 8 hom., cov: 33)
Exomes š‘“: 0.00058 ( 3 hom. )

Consequence

SFXN1
NM_022754.7 missense

Scores

1
17

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.356
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.010062873).
BP6
Variant 5-175492180-A-G is Benign according to our data. Variant chr5-175492180-A-G is described in ClinVar as [Benign]. Clinvar id is 783451.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0053 (808/152326) while in subpopulation AFR AF= 0.0187 (777/41576). AF 95% confidence interval is 0.0176. There are 8 homozygotes in gnomad4. There are 365 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SFXN1NM_022754.7 linkuse as main transcriptc.77A>G p.Asn26Ser missense_variant 2/11 ENST00000321442.10 NP_073591.2 Q9H9B4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SFXN1ENST00000321442.10 linkuse as main transcriptc.77A>G p.Asn26Ser missense_variant 2/111 NM_022754.7 ENSP00000316905.5 Q9H9B4

Frequencies

GnomAD3 genomes
AF:
0.00530
AC:
807
AN:
152208
Hom.:
8
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0187
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.00239
GnomAD3 exomes
AF:
0.00147
AC:
369
AN:
251370
Hom.:
2
AF XY:
0.00103
AC XY:
140
AN XY:
135868
show subpopulations
Gnomad AFR exome
AF:
0.0198
Gnomad AMR exome
AF:
0.000839
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000968
Gnomad OTH exome
AF:
0.000978
GnomAD4 exome
AF:
0.000583
AC:
852
AN:
1461798
Hom.:
3
Cov.:
31
AF XY:
0.000494
AC XY:
359
AN XY:
727194
show subpopulations
Gnomad4 AFR exome
AF:
0.0191
Gnomad4 AMR exome
AF:
0.00105
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000594
Gnomad4 OTH exome
AF:
0.00146
GnomAD4 genome
AF:
0.00530
AC:
808
AN:
152326
Hom.:
8
Cov.:
33
AF XY:
0.00490
AC XY:
365
AN XY:
74480
show subpopulations
Gnomad4 AFR
AF:
0.0187
Gnomad4 AMR
AF:
0.00131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.00237
Alfa
AF:
0.00106
Hom.:
2
Bravo
AF:
0.00643
ESP6500AA
AF:
0.0161
AC:
71
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.00174
AC:
211
Asia WGS
AF:
0.00144
AC:
5
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.000178

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpMar 29, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.051
BayesDel_addAF
Benign
-0.64
T
BayesDel_noAF
Benign
-0.67
CADD
Benign
6.1
DANN
Benign
0.92
DEOGEN2
Benign
0.0043
T;T;T;T
Eigen
Benign
-1.0
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.21
N
LIST_S2
Benign
0.79
T;T;T;T
MetaRNN
Benign
0.010
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.49
.;N;.;.
PrimateAI
Benign
0.25
T
PROVEAN
Benign
-0.36
N;N;.;N
REVEL
Benign
0.019
Sift
Benign
0.043
D;D;.;D
Sift4G
Uncertain
0.025
D;D;D;D
Polyphen
0.0
.;B;.;.
Vest4
0.075
MVP
0.21
MPC
0.17
ClinPred
0.0055
T
GERP RS
-3.0
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.0
Varity_R
0.052
gMVP
0.45

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.

Other links and lift over

dbSNP: rs17065105; hg19: chr5-174919183; COSMIC: COSV99072597; COSMIC: COSV99072597; API