rs1801109

Variant names:

• chr6-111674591-G-T
• rs1801109
• NM_002037.5:c.1313C>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_002037.5(FYN):​c.1313C>A​(p.Ala438Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FYN NM_002037.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.89
• Publications: 1 publications found

Genes affected

FYN (HGNC:4037): (FYN proto-oncogene, Src family tyrosine kinase) This gene is a member of the protein-tyrosine kinase oncogene family. It encodes a membrane-associated tyrosine kinase that has been implicated in the control of cell growth. The protein associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the fyn-binding protein. Alternatively spliced transcript variants encoding distinct isoforms exist. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.93

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002037.5. 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
	FYN	NM_002037.5	MANE Select	c.1313C>A	p.Ala438Asp	missense	Exon 13 of 14	NP_002028.1	P06241-1
	FYN	NM_001370529.1		c.1313C>A	p.Ala438Asp	missense	Exon 11 of 12	NP_001357458.1	P06241-1
	FYN	NM_153047.4		c.1304C>A	p.Ala435Asp	missense	Exon 13 of 14	NP_694592.1	P06241-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FYN	ENST00000354650.7	TSL:1 MANE Select	c.1313C>A	p.Ala438Asp	missense	Exon 13 of 14	ENSP00000346671.3	P06241-1
	FYN	ENST00000229471.8	TSL:1	c.1148C>A	p.Ala383Asp	missense	Exon 10 of 11	ENSP00000229471.4	P06241-3
	FYN	ENST00000905552.1		c.1469C>A	p.Ala490Asp	missense	Exon 12 of 13	ENSP00000575611.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.41	D
BayesDel_noAF	Pathogenic	0.35
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.92	D
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.93	D
MetaSVM	Uncertain	0.26	D
MutationAssessor	Benign	1.6	L
PhyloP100		9.9
PrimateAI	Pathogenic	0.90	D
PROVEAN	Pathogenic	-4.7	D
REVEL	Pathogenic	0.89
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.011	D
Polyphen		1.0	D
Vest4		0.91
MutPred		0.81		Gain of phosphorylation at Y440 (P = 0.0769)
MVP		0.96
MPC		2.8
ClinPred		0.99	D
GERP RS		5.7
Varity_R		0.99
gMVP		1.0
Mutation Taster		=11/89	disease causing

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

Other links and lift over

dbSNP: rs1801109; hg19: chr6-111995794;