5-122019291-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_152546.3(SRFBP1):​c.302C>T​(p.Ala101Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000453 in 1,612,254 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A101D) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000049 ( 0 hom. )

Consequence

SRFBP1
NM_152546.3 missense

Scores

9
6
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.53
Variant links:
Genes affected
SRFBP1 (HGNC:26333): (serum response factor binding protein 1) Enables RNA binding activity. Predicted to be involved in maturation of SSU-rRNA. Predicted to be located in perinuclear region of cytoplasm. Predicted to be part of 90S preribosome. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.788

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SRFBP1NM_152546.3 linkc.302C>T p.Ala101Val missense_variant Exon 5 of 8 ENST00000339397.5 NP_689759.2 Q8NEF9
SRFBP1XM_017009111.3 linkc.302C>T p.Ala101Val missense_variant Exon 5 of 8 XP_016864600.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SRFBP1ENST00000339397.5 linkc.302C>T p.Ala101Val missense_variant Exon 5 of 8 1 NM_152546.3 ENSP00000341324.4 Q8NEF9

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
152016
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000161
AC:
4
AN:
248744
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
134980
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:
0.0000354
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000486
AC:
71
AN:
1460238
Hom.:
0
Cov.:
30
AF XY:
0.0000385
AC XY:
28
AN XY:
726434
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:
0.0000585
Gnomad4 OTH exome
AF:
0.0000995
GnomAD4 genome
AF:
0.0000132
AC:
2
AN:
152016
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74234
show subpopulations
Gnomad4 AFR
AF:
0.0000241
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:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000225
Hom.:
0
Bravo
AF:
0.00000378
ExAC
AF:
0.00000828
AC:
1
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Nov 02, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.302C>T (p.A101V) alteration is located in exon 5 (coding exon 5) of the SRFBP1 gene. This alteration results from a C to T substitution at nucleotide position 302, causing the alanine (A) at amino acid position 101 to be replaced by a valine (V). 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
Uncertain
0.38
BayesDel_addAF
Pathogenic
0.24
D
BayesDel_noAF
Pathogenic
0.22
CADD
Pathogenic
28
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.30
T
Eigen
Pathogenic
0.88
Eigen_PC
Pathogenic
0.86
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.85
T
M_CAP
Benign
0.040
D
MetaRNN
Pathogenic
0.79
D
MetaSVM
Uncertain
0.027
D
MutationAssessor
Uncertain
2.5
M
PrimateAI
Uncertain
0.56
T
PROVEAN
Uncertain
-3.0
D
REVEL
Uncertain
0.34
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.78
MutPred
0.59
Gain of MoRF binding (P = 0.1017);
MVP
0.35
MPC
0.025
ClinPred
0.90
D
GERP RS
6.1
Varity_R
0.65
gMVP
0.60

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: rs544967694; hg19: chr5-121354986; API