Genetic Variant NM_005892.4:c.1640C>A (chr17-45241901-C-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_005892.4(FMNL1):c.1640C>A(p.Pro547Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000416 in 1,418,192 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000043 ( 0 hom. )

Consequence

FMNL1
NM_005892.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.07

Publications

0 publications found

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 links:

FMNL1-AS1 (HGNC:55717): (FMNL1 antisense RNA 1)

FMNL1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.17222852).

BS2

High AC in GnomAd4 at 5 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005892.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FMNL1	NM_005892.4	MANE Select	c.1640C>A	p.Pro547Gln	missense	Exon 15 of 27	NP_005883.3
FMNL1	NM_001411128.1		c.1640C>A	p.Pro547Gln	missense	Exon 15 of 26	NP_001398057.1	O95466-2
FMNL1-AS1	NR_186807.1		n.-131G>T		upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FMNL1	ENST00000331495.8	TSL:1 MANE Select	c.1640C>A	p.Pro547Gln	missense	Exon 15 of 27	ENSP00000329219.2	O95466-1
FMNL1	ENST00000587489.6	TSL:1	c.1640C>A	p.Pro547Gln	missense	Exon 15 of 26	ENSP00000465474.2	K7EK60
FMNL1	ENST00000947279.1		c.1658C>A	p.Pro553Gln	missense	Exon 17 of 28	ENSP00000617338.1

Frequencies

GnomAD3 genomes

AF:

0.0000330

AC:

AN:

151404

Hom.:

Cov.:

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:

0.0000740

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000347

AC:

AN:

28850

AF XY:

0.0000591

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000102

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000426

AC:

AN:

1266788

Hom.:

Cov.:

AF XY:

0.0000419

AC XY:

AN XY:

620496

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24638

American (AMR)

AF:

0.00

AC:

AN:

17192

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19042

East Asian (EAS)

AF:

0.00

AC:

AN:

28854

South Asian (SAS)

AF:

0.0000159

AC:

AN:

62950

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30712

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3590

European-Non Finnish (NFE)

AF:

0.0000487

AC:

AN:

1027576

Other (OTH)

AF:

0.0000574

AC:

AN:

52234

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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

AF:

0.0000330

AC:

AN:

151404

Hom.:

Cov.:

AF XY:

0.0000406

AC XY:

AN XY:

73868

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41308

American (AMR)

AF:

0.00

AC:

AN:

15226

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3456

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10522

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.0000740

AC:

AN:

67598

Other (OTH)

AF:

0.00

AC:

AN:

2076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000540

Hom.:

Bravo

AF:

0.0000113

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.33

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.48

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.1

PhyloP100

2.1

PrimateAI

Pathogenic

0.82

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.052

Sift

Benign

0.089

Sift4G

Uncertain

0.015

Polyphen

0.62

Vest4

0.34

MutPred

0.26

Loss of glycosylation at P547 (P = 0.0061)

MVP

0.24

MPC

0.54

ClinPred

0.19

GERP RS

3.2

Varity_R

0.12

gMVP

0.17

Mutation Taster

=88/12

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.19

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over