Genetic Variant SRFBP1:p.Ala177Glu (chr5-122020265-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_152546.3(SRFBP1):c.530C>A(p.Ala177Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,280 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A177V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SRFBP1
NM_152546.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0340

Publications

0 publications found

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]

SRFBP1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.337869).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152546.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRFBP1	NM_152546.3	MANE Select	c.530C>A	p.Ala177Glu	missense	Exon 6 of 8	NP_689759.2	Q8NEF9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SRFBP1	ENST00000339397.5	TSL:1 MANE Select	c.530C>A	p.Ala177Glu	missense	Exon 6 of 8	ENSP00000341324.4	Q8NEF9
SRFBP1	ENST00000959109.1		c.566C>A	p.Ala189Glu	missense	Exon 7 of 9	ENSP00000629168.1
SRFBP1	ENST00000919756.1		c.368C>A	p.Ala123Glu	missense	Exon 4 of 6	ENSP00000589815.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000809

AC:

AN:

247344

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000586

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.00000137

AC:

AN:

1460280

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726340

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33354

American (AMR)

AF:

0.0000450

AC:

AN:

44448

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26038

East Asian (EAS)

AF:

0.00

AC:

AN:

39650

South Asian (SAS)

AF:

0.00

AC:

AN:

85786

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53376

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5742

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111574

Other (OTH)

AF:

0.00

AC:

AN:

60312

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000828

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.026

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.62

M_CAP

Benign

0.0083

MetaRNN

Benign

0.34

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

PhyloP100

0.034

PrimateAI

Benign

0.30

PROVEAN

Benign

0.35

REVEL

Benign

0.16

Sift

Benign

0.23

Sift4G

Benign

0.87

Polyphen

0.96

Vest4

0.33

MutPred

0.75

Loss of MoRF binding (P = 0.0224)

MVP

0.22

MPC

0.010

ClinPred

0.14

GERP RS

2.6

Varity_R

0.051

gMVP

0.29

Mutation Taster

=89/11

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over