NM_182925.5:c.3985G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_182925.5(FLT4):​c.3985G>A​(p.Gly1329Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000316 in 1,614,020 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

FLT4
NM_182925.5 missense

Scores

9
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.53
Variant links:
Genes affected
FLT4 (HGNC:3767): (fms related receptor tyrosine kinase 4) This gene encodes a tyrosine kinase receptor for vascular endothelial growth factors C and D. The protein is thought to be involved in lymphangiogenesis and maintenance of the lymphatic endothelium. Mutations in this gene cause hereditary lymphedema type IA. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.24134651).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FLT4NM_182925.5 linkc.3985G>A p.Gly1329Ser missense_variant Exon 30 of 30 ENST00000261937.11 NP_891555.2 P35916-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FLT4ENST00000261937.11 linkc.3985G>A p.Gly1329Ser missense_variant Exon 30 of 30 1 NM_182925.5 ENSP00000261937.6 P35916-2
FLT4ENST00000502603.5 linkn.685G>A non_coding_transcript_exon_variant Exon 4 of 4 2

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152272
Hom.:
0
Cov.:
33
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:
0.000576
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000363
AC:
9
AN:
247796
Hom.:
0
AF XY:
0.0000149
AC XY:
2
AN XY:
134394
show subpopulations
Gnomad AFR exome
AF:
0.0000627
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000218
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000361
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000322
AC:
47
AN:
1461630
Hom.:
0
Cov.:
31
AF XY:
0.0000261
AC XY:
19
AN XY:
727096
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000227
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000324
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000262
AC:
4
AN:
152390
Hom.:
0
Cov.:
33
AF XY:
0.0000537
AC XY:
4
AN XY:
74526
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000578
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000386
Hom.:
0
Bravo
AF:
0.0000264
ExAC
AF:
0.0000494
AC:
6
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

ClinVar

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

Submissions by phenotype

not provided Uncertain:1
Jan 01, 2025
CeGaT Center for Human Genetics Tuebingen
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.066
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.29
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.19
T
Eigen
Uncertain
0.32
Eigen_PC
Uncertain
0.29
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Benign
0.69
T
M_CAP
Uncertain
0.23
D
MetaRNN
Benign
0.24
T
MetaSVM
Uncertain
0.019
D
MutationAssessor
Uncertain
2.5
M
PrimateAI
Benign
0.42
T
PROVEAN
Benign
-1.4
N
REVEL
Uncertain
0.37
Sift
Uncertain
0.0080
D
Sift4G
Benign
0.23
T
Polyphen
1.0
D
Vest4
0.13
MutPred
0.19
Gain of phosphorylation at G1329 (P = 0.015);
MVP
0.38
MPC
0.23
ClinPred
0.25
T
GERP RS
3.5
Varity_R
0.15
gMVP
0.40

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: rs765704568; hg19: chr5-180030299; COSMIC: COSV105855177; COSMIC: COSV105855177; API