FLT4 p.Ser1335Arg

Variant names:

• chr5-180603281-T-G
• NM_182925.5:c.4003A>C
• FLT4 p.Ser1335Arg

Your query was ambiguous. Multiple possible variants found:

• chr5-180603281-T-G
• chr5-180603279-G-T
• chr5-180603279-G-C
• chr5-180603279-GCT-ACG
• chr5-180603279-GCT-TCG
• chr5-180603279-GCT-CCG

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_182925.5(FLT4):​c.4003A>C​(p.Ser1335Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S1335S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FLT4 NM_182925.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.05
• Publications: 0 publications found

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]

FLT4 Gene-Disease associations (from GenCC):

• congenital heart defects, multiple types, 7

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae)
• lymphatic malformation 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• capillary infantile hemangioma

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• lymphatic malformation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• tetralogy of fallot

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22939038).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182925.5. 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
	FLT4	NM_182925.5	MANE Select	c.4003A>C	p.Ser1335Arg	missense	Exon 30 of 30	NP_891555.2	P35916-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLT4	ENST00000261937.11	TSL:1 MANE Select	c.4003A>C	p.Ser1335Arg	missense	Exon 30 of 30	ENSP00000261937.6	P35916-2
	FLT4	ENST00000955857.1		c.4279A>C	p.Ser1427Arg	missense	Exon 30 of 30	ENSP00000625916.1
	FLT4	ENST00000861588.1		c.4069A>C	p.Ser1357Arg	missense	Exon 30 of 30	ENSP00000531647.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.027	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.88	D
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.39	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		5.0
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.38
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.0080	D
Varity_R		0.32
gMVP		0.34
Mutation Taster		=63/37	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr5-180030281;