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GeneBe

1-26863457-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_006142.5(SFN):c.245G>A(p.Arg82His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000031 in 1,614,004 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

SFN
NM_006142.5 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.629
Variant links:
Genes affected
SFN (HGNC:10773): (stratifin) This gene encodes a cell cycle checkpoint protein. The encoded protein binds to translation and initiation factors and functions as a regulator of mitotic translation. In response to DNA damage this protein plays a role in preventing DNA errors during mitosis. [provided by RefSeq, Aug 2017]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.10436821).
BS2
High AC in GnomAd at 5 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SFNNM_006142.5 linkuse as main transcriptc.245G>A p.Arg82His missense_variant 1/1 ENST00000339276.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SFNENST00000339276.6 linkuse as main transcriptc.245G>A p.Arg82His missense_variant 1/1 NM_006142.5 P1P31947-1

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152156
Hom.:
0
Cov.:
32
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:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250734
Hom.:
0
AF XY:
0.00000738
AC XY:
1
AN XY:
135534
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:
0.00
Gnomad NFE exome
AF:
0.00000884
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000308
AC:
45
AN:
1461848
Hom.:
0
Cov.:
33
AF XY:
0.0000275
AC XY:
20
AN XY:
727224
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:
0.0000387
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152156
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74332
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:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000579
Hom.:
0
Bravo
AF:
0.0000302

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 submitterclinical testingAmbry GeneticsDec 07, 2021The c.245G>A (p.R82H) alteration is located in exon 1 (coding exon 1) of the SFN gene. This alteration results from a G to A substitution at nucleotide position 245, causing the arginine (R) at amino acid position 82 to be replaced by a histidine (H). 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
0.12
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.57
Cadd
Benign
17
Dann
Uncertain
0.99
DEOGEN2
Uncertain
0.47
T
Eigen
Benign
-0.84
Eigen_PC
Benign
-0.84
FATHMM_MKL
Benign
0.082
N
LIST_S2
Benign
0.80
T
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.10
T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
1.8
L
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.19
T
PROVEAN
Uncertain
-3.0
D
REVEL
Benign
0.062
Sift
Uncertain
0.010
D
Sift4G
Uncertain
0.038
D
Polyphen
0.019
B
Vest4
0.10
MVP
0.23
MPC
0.84
ClinPred
0.21
T
GERP RS
-1.6
Varity_R
0.35
gMVP
0.24

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs923826779; hg19: chr1-27189948; API