chr5-180603307-G-A

Position:

• chr5-180603307-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_182925.5(FLT4):​c.3977C>T​(p.Ala1326Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: FLT4 NM_182925.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.46

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]

ACMG classification

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=0.045718014).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLT4	NM_182925.5	c.3977C>T	p.Ala1326Val	missense_variant	30/30	ENST00000261937.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLT4	ENST00000261937.11	c.3977C>T	p.Ala1326Val	missense_variant	30/30	1	NM_182925.5	P1
FLT4	ENST00000502603.5	n.677C>T		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Revvity Omics, Revvity

May 19, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.085	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.096	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.3	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.55	N
REVEL	Benign	0.17
Sift	Benign	0.16	T
Sift4G	Benign	0.63	T
Polyphen		0.0020	B
Vest4		0.039
MutPred		0.15		Gain of MoRF binding (P = 0.1202);
MVP		0.22
MPC		0.11
ClinPred		0.17	T
GERP RS		-1.0
Varity_R		0.036
gMVP		0.15

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-180030307;