NM_002031.3:c.805A>C

Variant names:

• chr6-115956605-T-G
• NM_002031.3:c.805A>C
• FRK p.Met269Leu

Variant summary

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

The NM_002031.3(FRK):​c.805A>C​(p.Met269Leu) 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M269V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FRK NM_002031.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.02
• Publications: 0 publications found

Genes affected

FRK (HGNC:3955): (fyn related Src family tyrosine kinase) The protein encoded by this gene belongs to the TYR family of protein kinases. This tyrosine kinase is a nuclear protein and may function during G1 and S phase of the cell cycle and suppress growth. [provided by RefSeq, Jul 2008]

ENSG00000289376 (HGNC:):

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, 0.908

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002031.3. 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
	FRK	NM_002031.3	MANE Select	c.805A>C	p.Met269Leu	missense	Exon 5 of 8	NP_002022.1	P42685-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRK	ENST00000606080.2	TSL:1 MANE Select	c.805A>C	p.Met269Leu	missense	Exon 5 of 8	ENSP00000476145.1	P42685-1
	FRK	ENST00000891227.1		c.805A>C	p.Met269Leu	missense	Exon 6 of 9	ENSP00000561286.1
	FRK	ENST00000891226.1		c.757A>C	p.Met253Leu	missense	Exon 5 of 8	ENSP00000561285.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.54	D
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.036	D
MetaRNN	Pathogenic	0.91	D
MetaSVM	Uncertain	0.14	D
MutationAssessor	Benign	-0.28	N
PhyloP100		8.0
PrimateAI	Uncertain	0.60	T
Sift4G	Benign	0.091	T
Varity_R		0.77
gMVP		0.53
Mutation Taster		=29/71	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

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

Other links and lift over

hg19: chr6-116277768;