17-45222176-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_005892.4(FMNL1):​c.52C>T​(p.Pro18Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000163 in 1,226,546 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 9.3e-7 ( 0 hom. )

Consequence

FMNL1
NM_005892.4 missense

Scores

1
1
16

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0790
Variant links:
Genes affected
FMNL1 (HGNC:1212): (formin like 1) This gene encodes a formin-related protein. Formin-related proteins have been implicated in morphogenesis, cytokinesis, and cell polarity. An alternative splice variant has been described but its full length sequence has not been determined. [provided by RefSeq, Jul 2008]
FMNL1-DT (HGNC:55311): (FMNL1 divergent transcript)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.14130628).
BP6
Variant 17-45222176-C-T is Benign according to our data. Variant chr17-45222176-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2262615.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FMNL1NM_005892.4 linkc.52C>T p.Pro18Ser missense_variant Exon 1 of 27 ENST00000331495.8 NP_005883.3 O95466-1
FMNL1NM_001411128.1 linkc.52C>T p.Pro18Ser missense_variant Exon 1 of 26 NP_001398057.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FMNL1ENST00000331495.8 linkc.52C>T p.Pro18Ser missense_variant Exon 1 of 27 1 NM_005892.4 ENSP00000329219.2 O95466-1

Frequencies

GnomAD3 genomes
AF:
0.00000664
AC:
1
AN:
150526
Hom.:
0
Cov.:
31
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:
0.00
Gnomad OTH
AF:
0.000484
GnomAD4 exome
AF:
9.29e-7
AC:
1
AN:
1076020
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
518642
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:
0.00000109
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000664
AC:
1
AN:
150526
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
73470
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:
0.00
Gnomad4 OTH
AF:
0.000484

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Nov 30, 2021
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.060
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
4.9
DANN
Benign
0.92
DEOGEN2
Benign
0.016
T;T
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.016
N
LIST_S2
Benign
0.37
T;T
M_CAP
Pathogenic
0.69
D
MetaRNN
Benign
0.14
T;T
MetaSVM
Benign
-0.96
T
PrimateAI
Uncertain
0.77
T
PROVEAN
Benign
-0.48
N;N
REVEL
Benign
0.24
Sift
Benign
0.49
T;T
Sift4G
Benign
0.19
T;T
Polyphen
0.0
B;.
Vest4
0.098
MutPred
0.26
Gain of phosphorylation at P18 (P = 0.0059);Gain of phosphorylation at P18 (P = 0.0059);
MVP
0.43
MPC
0.59
ClinPred
0.042
T
GERP RS
-3.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
3.2
Varity_R
0.024
gMVP
0.17

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: rs1001732920; hg19: chr17-43299543; API