rs1454761319

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

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

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>C​(p.Met317Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: FER NM_005246.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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=0.08400139).

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>C	p.Met317Thr	missense	Exon 9 of 20	NP_005237.2	P16591-1
	FER	NM_001308028.2		c.425T>C	p.Met142Thr	missense	Exon 7 of 18	NP_001294957.1	P16591-2
	FER	NR_146155.2		n.1055T>C		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>C	p.Met317Thr	missense	Exon 9 of 20	ENSP00000281092.4	P16591-1
	FER	ENST00000880768.1		c.950T>C	p.Met317Thr	missense	Exon 9 of 20	ENSP00000550827.1
	FER	ENST00000880770.1		c.950T>C	p.Met317Thr	missense	Exon 8 of 19	ENSP00000550829.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455856 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 724158

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33216

American (AMR) AF: 0.00 AC: 0 AN: 44242

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25892

East Asian (EAS) AF: 0.00 AC: 0 AN: 39460

South Asian (SAS) AF: 0.00 AC: 0 AN: 85464

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53306

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5738

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1108460

Other (OTH) AF: 0.00 AC: 0 AN: 60078

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	15
DANN	Benign	0.79
DEOGEN2	Benign	0.073	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.084	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.050	N
PhyloP100		1.3
PrimateAI	Benign	0.46	T
PROVEAN	Benign	0.25	N
REVEL	Benign	0.070
Sift	Benign	0.52	T
Sift4G	Benign	0.58	T
Polyphen		0.0	B
Vest4		0.30
MutPred		0.26		Loss of catalytic residue at M317 (P = 0.0335)
MVP		0.31
MPC		0.20
ClinPred		0.095	T
GERP RS		4.3
Varity_R		0.044
gMVP		0.18
Mutation Taster		=91/9	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;