rs1454761319

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr5-108883422-T-A
• chr5-108883422-T-C
• chr5-108883422-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 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. 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. 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

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.113072455).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FER	NM_005246.4	c.950T>A	p.Met317Lys	missense_variant	Exon 9 of 20	ENST00000281092.9	NP_005237.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FER	ENST00000281092.9	c.950T>A	p.Met317Lys	missense_variant	Exon 9 of 20	1	NM_005246.4	ENSP00000281092.4
FER	ENST00000504143.6	n.*421T>A		non_coding_transcript_exon_variant	Exon 7 of 18	5		ENSP00000421951.2
FER	ENST00000504143.6	n.*421T>A		3_prime_UTR_variant	Exon 7 of 18	5		ENSP00000421951.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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
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

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

LitVar

Other links and lift over

dbSNP: rs1454761319; hg19: chr5-108219123;