Variant 8-123975912-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2

The NM_001039112.2(FER1L6):c.698C>T(p.Pro233Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00008 in 1,600,740 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000081 ( 4 hom. )

Consequence

FER1L6
NM_001039112.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.91

Variant links:

Genes affected

FER1L6 (HGNC:28065): (fer-1 like family member 6) Predicted to enable metal ion binding activity. Predicted to be involved in plasma membrane organization. Predicted to act upstream of or within response to bacterium. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

FER1L6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.888

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FER1L6	NM_001039112.2 link	c.698C>T	p.Pro233Leu	missense_variant	9/41	ENST00000522917.5	NP_001034201.2	Q2WGJ9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FER1L6	ENST00000522917.5 link	c.698C>T	p.Pro233Leu	missense_variant	9/41	1	NM_001039112.2	ENSP00000428280.1		Q2WGJ9

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000772

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000111

AC:

AN:

243436

Hom.:

AF XY:

0.0000682

AC XY:

AN XY:

131898

show subpopulations

Gnomad AFR exome

AF:

0.0000656

Gnomad AMR exome

AF:

0.0000902

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000740

Gnomad SAS exome

AF:

0.000206

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000682

GnomAD4 exome

AF:

0.0000815

AC:

118

AN:

1448646

Hom.:

Cov.:

AF XY:

0.0000695

AC XY:

AN XY:

719546

show subpopulations

Gnomad4 AFR exome

AF:

0.0000605

Gnomad4 AMR exome

AF:

0.0000685

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000458

Gnomad4 SAS exome

AF:

0.0000722

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.05e-7

Gnomad4 OTH exome

AF:

0.00147

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152094

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000772

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000956

Alfa

AF:

0.000174

Hom.:

Bravo

AF:

0.0000831

ExAC

AF:

0.000149

AC:

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 26, 2021

The c.698C>T (p.P233L) alteration is located in exon 8 (coding exon 8) of the FER1L6 gene. This alteration results from a C to T substitution at nucleotide position 698, causing the proline (P) at amino acid position 233 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.67

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Pathogenic

0.40

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.30

Eigen

Pathogenic

0.83

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

M_CAP

Uncertain

0.16

MetaRNN

Pathogenic

0.89

MetaSVM

Pathogenic

1.0

MutationAssessor

Pathogenic

3.6

PrimateAI

Uncertain

0.70

PROVEAN

Pathogenic

-9.5

REVEL

Pathogenic

0.73

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.89

MutPred

0.76

Loss of disorder (P = 0.0662);

MVP

0.46

MPC

0.54

ClinPred

0.99

GERP RS

6.0

Varity_R

0.76

gMVP

0.67

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over