5-108883422-T-A

Variant names:

• chr5-108883422-T-A
• rs1454761319
• NM_005246.4:c.950T>A

Variant summary

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

The NM_005246.4(FER):​c.950T>A​(p.Met317Lys) 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. 17/22 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. M317T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FER NM_005246.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33
• Publications: 0 publications found

Genes affected

FER (HGNC:3655): (FER tyrosine kinase) The protein encoded by this gene is a member of the FPS/FES family of non-transmembrane receptor tyrosine kinases. It regulates cell-cell adhesion and mediates signaling from the cell surface to the cytoskeleton via growth factor receptors. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome X. [provided by RefSeq, Apr 2015]

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=0.113072455).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005246.4. 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
	FER	NM_005246.4	MANE Select	c.950T>A	p.Met317Lys	missense	Exon 9 of 20	NP_005237.2	P16591-1
	FER	NM_001308028.2		c.425T>A	p.Met142Lys	missense	Exon 7 of 18	NP_001294957.1	P16591-2
	FER	NR_146155.2		n.1055T>A		non_coding_transcript_exon	Exon 8 of 20

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FER	ENST00000281092.9	TSL:1 MANE Select	c.950T>A	p.Met317Lys	missense	Exon 9 of 20	ENSP00000281092.4	P16591-1
	FER	ENST00000880768.1		c.950T>A	p.Met317Lys	missense	Exon 9 of 20	ENSP00000550827.1
	FER	ENST00000880770.1		c.950T>A	p.Met317Lys	missense	Exon 8 of 19	ENSP00000550829.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.067	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	16
DANN	Benign	0.66
DEOGEN2	Benign	0.068	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.3
PrimateAI	Benign	0.42	T
PROVEAN	Benign	0.80	N
REVEL	Benign	0.19
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.53
MutPred		0.42		Gain of ubiquitination at M317 (P = 0.0045)
MVP		0.60
MPC		0.28
ClinPred		0.041	T
GERP RS		4.3
Varity_R		0.16
gMVP		0.26
Mutation Taster		=84/16	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

Other links and lift over

dbSNP: rs1454761319; hg19: chr5-108219123;