2-96651928-G-T

Position:

• chr2-96651928-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001293083.2(FER1L5):​c.541G>T​(p.Gly181Cys) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: FER1L5 NM_001293083.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.62

Genes affected

FER1L5 (HGNC:19044): (fer-1 like family member 5) Predicted to enable calcium ion binding activity and calcium-dependent phospholipid binding activity. Predicted to be involved in several processes, including myeloid cell activation involved in immune response; negative regulation of phagocytosis; and plasma membrane organization. Predicted to be located in plasma membrane. Predicted to be integral component of membrane. Predicted to be active in T-tubule and cytoplasmic vesicle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.852

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FER1L5	NM_001293083.2	c.541G>T	p.Gly181Cys	missense_variant	7/53	ENST00000624922.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FER1L5	ENST00000624922.6	c.541G>T	p.Gly181Cys	missense_variant	7/53	5	NM_001293083.2	P4
FER1L5	ENST00000623019.5	c.541G>T	p.Gly181Cys	missense_variant	7/52			A2
FER1L5	ENST00000505256.6	n.549G>T		non_coding_transcript_exon_variant	6/6	2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	28
DANN	Benign	0.91
Eigen	Pathogenic	0.97
Eigen_PC	Pathogenic	0.93
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D;D;D
MetaRNN	Pathogenic	0.85	D;D;D
MetaSVM	Uncertain	0.22	D
PrimateAI	Uncertain	0.57	T
Polyphen		1.0	.;D;.
Vest4		0.69, 0.65
MutPred		0.54		Loss of MoRF binding (P = 0.0769);Loss of MoRF binding (P = 0.0769);Loss of MoRF binding (P = 0.0769);
MVP		0.56
ClinPred		1.0	D
GERP RS		5.7
Varity_R		0.44
gMVP		0.73

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-97317665;