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GeneBe

2-38748122-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001031684.3(SRSF7):c.497T>C(p.Ile166Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000223 in 1,613,948 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 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

SRSF7
NM_001031684.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.74
Variant links:
Genes affected
SRSF7 (HGNC:10789): (serine and arginine rich splicing factor 7) The protein encoded by this gene is a member of the serine/arginine (SR)-rich family of pre-mRNA splicing factors, which constitute part of the spliceosome. Each of these factors contains an N-terminal RNA recognition motif (RRM) for binding RNA and a C-terminal RS domain for binding other proteins. The RS domain is rich in serine and arginine residues and facilitates interaction between different SR splicing factors. In addition to being critical for mRNA splicing, the SR proteins have also been shown to be involved in mRNA export from the nucleus and in translation. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2018]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.01337713).
BS2
High AC in GnomAd4 at 8 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SRSF7NM_001031684.3 linkuse as main transcriptc.497T>C p.Ile166Thr missense_variant 5/8 ENST00000313117.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SRSF7ENST00000313117.11 linkuse as main transcriptc.497T>C p.Ile166Thr missense_variant 5/81 NM_001031684.3 P4Q16629-1

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152142
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000328
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000398
AC:
10
AN:
251436
Hom.:
0
AF XY:
0.0000515
AC XY:
7
AN XY:
135896
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000260
Gnomad ASJ exome
AF:
0.0000992
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000192
AC:
28
AN:
1461692
Hom.:
0
Cov.:
31
AF XY:
0.0000193
AC XY:
14
AN XY:
727136
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000224
Gnomad4 ASJ exome
AF:
0.0000765
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000540
Gnomad4 OTH exome
AF:
0.000166
GnomAD4 genome
AF:
0.0000525
AC:
8
AN:
152256
Hom.:
0
Cov.:
32
AF XY:
0.0000403
AC XY:
3
AN XY:
74450
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.000327
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000529
ExAC
AF:
0.0000412
AC:
5

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 GeneticsAug 16, 2022The c.497T>C (p.I166T) alteration is located in exon 5 (coding exon 5) of the SRSF7 gene. This alteration results from a T to C substitution at nucleotide position 497, causing the isoleucine (I) at amino acid position 166 to be replaced by a threonine (T). 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
0.17
BayesDel_addAF
Benign
-0.42
T
BayesDel_noAF
Benign
-0.55
CADD
Uncertain
24
DANN
Benign
0.94
DEOGEN2
Benign
0.028
T;.;.
Eigen
Benign
-0.64
Eigen_PC
Benign
-0.44
FATHMM_MKL
Benign
0.56
D
LIST_S2
Benign
0.75
T;T;T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.013
T;T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
0.14
N;N;.
MutationTaster
Benign
0.98
N;N;N
PrimateAI
Uncertain
0.52
T
PROVEAN
Benign
0.44
N;N;N
REVEL
Benign
0.054
Sift
Benign
0.99
T;T;T
Sift4G
Benign
0.60
T;T;T
Polyphen
0.0020
B;.;.
Vest4
0.19
MutPred
0.36
Gain of phosphorylation at I166 (P = 0.0031);Gain of phosphorylation at I166 (P = 0.0031);Gain of phosphorylation at I166 (P = 0.0031);
MVP
0.14
MPC
0.60
ClinPred
0.086
T
GERP RS
3.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.071
gMVP
0.38

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.090
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-38975264; API