8-123966166-T-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001039112.2(FER1L6):c.260T>A(p.Ile87Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00759 in 1,614,006 control chromosomes in the GnomAD database, including 73 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0060 (7 hom., cov: 32)
  • Exomes 𝑓: 0.0078 (66 hom.)
• Consequence: FER1L6 NM_001039112.2 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 7.99

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.017080188).
• BP6: Variant 8-123966166-T-A is Benign according to our data. Variant chr8-123966166-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 789300.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FER1L6	NM_001039112.2	c.260T>A	p.Ile87Lys	missense_variant	5/41	ENST00000522917.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FER1L6	ENST00000522917.5	c.260T>A	p.Ile87Lys	missense_variant	5/41	1	NM_001039112.2	P1

Frequencies

GnomAD3 genomes AF: 0.00598 AC: 910 AN: 152142 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.00159

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.00471

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00415

Gnomad FIN AF: 0.00924

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00920

Gnomad OTH AF: 0.00908

GnomAD3 exomes AF: 0.00630 AC: 1568 AN: 249032 Hom.: 7 AF XY: 0.00665 AC XY: 898 AN XY: 135096

Gnomad AFR exome AF: 0.00129

Gnomad AMR exome AF: 0.00458

Gnomad ASJ exome AF: 0.00189

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00481

Gnomad FIN exome AF: 0.00933

Gnomad NFE exome AF: 0.00870

Gnomad OTH exome AF: 0.00662

GnomAD4 exome AF: 0.00776 AC: 11339 AN: 1461746 Hom.: 66 Cov.: 31 AF XY: 0.00768 AC XY: 5586 AN XY: 727158

Gnomad4 AFR exome AF: 0.00105

Gnomad4 AMR exome AF: 0.00465

Gnomad4 ASJ exome AF: 0.00142

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00441

Gnomad4 FIN exome AF: 0.00957

Gnomad4 NFE exome AF: 0.00871

Gnomad4 OTH exome AF: 0.00745

GnomAD4 genome AF: 0.00598 AC: 910 AN: 152260 Hom.: 7 Cov.: 32 AF XY: 0.00575 AC XY: 428 AN XY: 74440

Gnomad4 AFR AF: 0.00159

Gnomad4 AMR AF: 0.00471

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00415

Gnomad4 FIN AF: 0.00924

Gnomad4 NFE AF: 0.00920

Gnomad4 OTH AF: 0.00899

Alfa AF: 0.00753 Hom.: 3

Bravo AF: 0.00509

TwinsUK AF: 0.0111 AC: 41

ALSPAC AF: 0.00752 AC: 29

ESP6500AA AF: 0.00119 AC: 5

ESP6500EA AF: 0.00780 AC: 66

ExAC AF: 0.00615 AC: 745

Asia WGS AF: 0.00375 AC: 14 AN: 3478

EpiCase AF: 0.00698

EpiControl AF: 0.00682

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2023	FER1L6: BS2 -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Benign	-0.047	T
BayesDel_noAF	Pathogenic	0.17
Cadd	Uncertain	24
Dann	Benign	0.96
DEOGEN2	Benign	0.34	T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D
MetaRNN	Benign	0.017	T
MetaSVM	Uncertain	0.098	D
MutationAssessor	Pathogenic	3.0	M
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.58	T
PROVEAN	Pathogenic	-6.1	D
REVEL	Pathogenic	0.83
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.97	D
Vest4		0.90
MVP		0.46
MPC		0.68
ClinPred		0.045	T
GERP RS		5.3
Varity_R		0.82
gMVP		0.87

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: rs74808242; hg19: chr8-124978406;