5-122020100-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152546.3(SRFBP1):​c.365C>A​(p.Ala122Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000102 in 1,565,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000099 ( 0 hom. )

Consequence

SRFBP1
NM_152546.3 missense

Scores

1
6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.57
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.18291566).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SRFBP1NM_152546.3 linkc.365C>A p.Ala122Asp missense_variant Exon 6 of 8 ENST00000339397.5 NP_689759.2 Q8NEF9
SRFBP1XM_017009111.3 linkc.365C>A p.Ala122Asp missense_variant Exon 6 of 8 XP_016864600.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SRFBP1ENST00000339397.5 linkc.365C>A p.Ala122Asp missense_variant Exon 6 of 8 1 NM_152546.3 ENSP00000341324.4 Q8NEF9

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
152024
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000532
AC:
11
AN:
206872
Hom.:
0
AF XY:
0.0000450
AC XY:
5
AN XY:
111168
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000408
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000991
AC:
14
AN:
1412948
Hom.:
0
Cov.:
30
AF XY:
0.00000858
AC XY:
6
AN XY:
699014
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000388
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:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152142
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74362
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000378
ExAC
AF:
0.0000580
AC:
7
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 26, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.365C>A (p.A122D) alteration is located in exon 6 (coding exon 6) of the SRFBP1 gene. This alteration results from a C to A substitution at nucleotide position 365, causing the alanine (A) at amino acid position 122 to be replaced by an aspartic acid (D). 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
-0.21
T
BayesDel_noAF
Benign
-0.22
CADD
Benign
22
DANN
Uncertain
0.98
DEOGEN2
Benign
0.067
T
Eigen
Uncertain
0.46
Eigen_PC
Uncertain
0.40
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.69
T
M_CAP
Benign
0.018
T
MetaRNN
Benign
0.18
T
MetaSVM
Uncertain
-0.20
T
MutationAssessor
Uncertain
2.3
M
PrimateAI
Benign
0.47
T
PROVEAN
Benign
-1.2
N
REVEL
Benign
0.21
Sift
Benign
0.15
T
Sift4G
Uncertain
0.0030
D
Polyphen
0.99
D
Vest4
0.29
MutPred
0.56
Loss of MoRF binding (P = 0.0475);
MVP
0.60
MPC
0.0068
ClinPred
0.36
T
GERP RS
5.1
Varity_R
0.29
gMVP
0.52

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: rs373773092; hg19: chr5-121355795; API