rs6030

Variant names:

• chr1-169529737-T-A
• NM_000130.5:c.5290A>T

Your query was ambiguous. Multiple possible variants found:

• chr1-169529737-T-A
• chr1-169529737-T-C
• chr1-169529737-T-G

Variant summary

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

The NM_000130.5(F5):​c.5290A>T​(p.Met1764Leu) 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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M1764V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: F5 NM_000130.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27

Genes affected

F5 (HGNC:3542): (coagulation factor V) This gene encodes an essential cofactor of the blood coagulation cascade. This factor circulates in plasma, and is converted to the active form by the release of the activation peptide by thrombin during coagulation. This generates a heavy chain and a light chain which are held together by calcium ions. The activated protein is a cofactor that participates with activated coagulation factor X to activate prothrombin to thrombin. Defects in this gene result in either an autosomal recessive hemorrhagic diathesis or an autosomal dominant form of thrombophilia, which is known as activated protein C resistance. [provided by RefSeq, Oct 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=0.028760672).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F5	NM_000130.5	c.5290A>T	p.Met1764Leu	missense_variant	Exon 16 of 25	ENST00000367797.9	NP_000121.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
F5	ENST00000367797.9	c.5290A>T	p.Met1764Leu	missense_variant	Exon 16 of 25	1	NM_000130.5	ENSP00000356771.3
F5	ENST00000367796.3	c.5305A>T	p.Met1769Leu	missense_variant	Exon 16 of 25	5		ENSP00000356770.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	0.10
DANN	Benign	0.75
DEOGEN2	Benign	0.014	T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.051	N
LIST_S2	Benign	0.048	T;T
M_CAP	Benign	0.071	D
MetaRNN	Benign	0.029	T;T
MetaSVM	Benign	-0.33	T
MutationAssessor	Benign	-0.80	N;.
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.050	N;N
REVEL	Benign	0.25
Sift	Benign	0.41	T;T
Sift4G	Benign	0.71	T;T
Polyphen		0.0	B;.
Vest4		0.050
MutPred		0.39		Loss of disorder (P = 0.1197);.;
MVP		0.47
MPC		0.080
ClinPred		0.051	T
GERP RS		-2.9
Varity_R		0.16
gMVP		0.56

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: chr1-169498975;