Genetic Variant FNBP1L:p.Thr343Pro (chr1-93536368-A-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001164473.3(FNBP1L):c.1027A>C(p.Thr343Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000142 in 1,548,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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: 0.000014 ( 0 hom. )

Consequence

FNBP1L
NM_001164473.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.52

Publications

0 publications found

Variant links:

Genes affected

FNBP1L (HGNC:20851): (formin binding protein 1 like) The protein encoded by this gene binds to both CDC42 and N-WASP. This protein promotes CDC42-induced actin polymerization by activating the N-WASP-WIP complex and, therefore, is involved in a pathway that links cell surface signals to the actin cytoskeleton. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

FNBP1L links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06686884).

BS2

High AC in GnomAdExome4 at 20 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164473.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FNBP1L	NM_001164473.3	MANE Select	c.1027A>C	p.Thr343Pro	missense	Exon 10 of 17	NP_001157945.1	Q5T0N5-1
FNBP1L	NM_001024948.3		c.990+1460A>C		intron	N/A	NP_001020119.1	Q5T0N5-4
FNBP1L	NM_017737.5		c.990+1460A>C		intron	N/A	NP_060207.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FNBP1L	ENST00000271234.13	TSL:5 MANE Select	c.1027A>C	p.Thr343Pro	missense	Exon 10 of 17	ENSP00000271234.7	Q5T0N5-1
FNBP1L	ENST00000260506.12	TSL:1	c.990+1460A>C		intron	N/A	ENSP00000260506.8	Q5T0N5-4
FNBP1L	ENST00000868905.1		c.1027A>C	p.Thr343Pro	missense	Exon 10 of 16	ENSP00000538964.1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151990

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000192

AC:

AN:

156576

AF XY:

0.0000121

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:

0.0000492

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000143

AC:

AN:

1396770

Hom.:

Cov.:

AF XY:

0.0000116

AC XY:

AN XY:

688992

show subpopulations

African (AFR)

AF:

0.0000318

AC:

AN:

31490

American (AMR)

AF:

0.00

AC:

AN:

35280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25094

East Asian (EAS)

AF:

0.00

AC:

AN:

35616

South Asian (SAS)

AF:

0.00

AC:

AN:

78822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49356

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5690

European-Non Finnish (NFE)

AF:

0.0000176

AC:

AN:

1077498

Other (OTH)

AF:

0.00

AC:

AN:

57924

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.0000132

AC:

AN:

151990

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74252

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41382

American (AMR)

AF:

0.00

AC:

AN:

15234

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

67966

Other (OTH)

AF:

0.00

AC:

AN:

2092

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

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:

0.0000778

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000394

AC:

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

0.049

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.32

DEOGEN2

Benign

0.024

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.10

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.46

M_CAP

Benign

0.0085

MetaRNN

Benign

0.067

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-1.6

PhyloP100

3.5

PrimateAI

Uncertain

0.62

PROVEAN

Benign

1.8

REVEL

Benign

0.18

Sift

Benign

1.0

Sift4G

Benign

0.57

Vest4

0.20

MutPred

0.15

Gain of glycosylation at T346 (P = 0.1227)

MVP

0.48

MPC

0.47

ClinPred

0.060

GERP RS

5.2

Varity_R

0.20

gMVP

0.31

Mutation Taster

=66/34

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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