Variant chr1-169851821-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001320047.2(FIRRM):c.2249G>A(p.Gly750Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00373 in 1,613,748 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 4 hom., cov: 31)

Exomes 𝑓: 0.0038 ( 23 hom. )

Consequence

FIRRM
NM_001320047.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.02

Variant links:

Genes affected

FIRRM (HGNC:25565): (FIGNL1 interacting regulator of recombination and mitosis)

FIRRM links:

SCYL3 (HGNC:19285): (SCY1 like pseudokinase 3) This gene encodes a protein with a kinase domain and four HEAT repeats. The encoded protein interacts with the C-terminal domain of ezrin, an ERM protein, and may play a role in cell adhesion and migration. Alternative splicing results in multiple transcript variants encoding multiple isoforms. [provided by RefSeq, Jun 2012]

SCYL3 links:

C1orf112 (HGNC:):

C1orf112 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004492849).

BP6

Variant 1-169851821-G-A is Benign according to our data. Variant chr1-169851821-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2639542.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FIRRM	NM_001320047.2 linkuse as main transcript	c.2249G>A	p.Gly750Glu	missense_variant	24/25	ENST00000359326.9	NP_001306976.1	Q9NSG2-1A0A024R922
SCYL3	NM_020423.7 linkuse as main transcript	c.*1892C>T		3_prime_UTR_variant	13/13	ENST00000367771.11	NP_065156.5	Q8IZE3-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C1orf112	ENST00000359326.9 linkuse as main transcript	c.2249G>A	p.Gly750Glu	missense_variant	24/25	1	NM_001320047.2	ENSP00000352276.4		Q9NSG2-1
SCYL3	ENST00000367771 linkuse as main transcript	c.*1892C>T		3_prime_UTR_variant	13/13	1	NM_020423.7	ENSP00000356745.5		Q8IZE3-2

Frequencies

GnomAD3 genomes

AF:

0.00274

AC:

416

AN:

152046

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000652

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000721

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00332

Gnomad FIN

AF:

0.00340

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00466

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00297

AC:

746

AN:

251100

Hom.:

AF XY:

0.00315

AC XY:

428

AN XY:

135706

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.000897

Gnomad ASJ exome

AF:

0.00139

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00324

Gnomad FIN exome

AF:

0.00436

Gnomad NFE exome

AF:

0.00422

Gnomad OTH exome

AF:

0.00376

GnomAD4 exome

AF:

0.00384

AC:

5611

AN:

1461584

Hom.:

Cov.:

AF XY:

0.00391

AC XY:

2843

AN XY:

727092

show subpopulations

Gnomad4 AFR exome

AF:

0.000448

Gnomad4 AMR exome

AF:

0.000738

Gnomad4 ASJ exome

AF:

0.00142

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00383

Gnomad4 FIN exome

AF:

0.00489

Gnomad4 NFE exome

AF:

0.00428

Gnomad4 OTH exome

AF:

0.00267

GnomAD4 genome

AF:

0.00273

AC:

416

AN:

152164

Hom.:

Cov.:

AF XY:

0.00254

AC XY:

189

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.000650

Gnomad4 AMR

AF:

0.000720

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00332

Gnomad4 FIN

AF:

0.00340

Gnomad4 NFE

AF:

0.00466

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00373

Hom.:

Bravo

AF:

0.00237

TwinsUK

AF:

0.00405

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00488

AC:

ExAC

AF:

0.00316

AC:

384

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00496

EpiControl

AF:

0.00397

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

FIRRM: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.0072

T;T;.

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.64

.;T;T

M_CAP

Benign

0.0055

MetaRNN

Benign

0.0045

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;L;.

PROVEAN

Benign

0.040

N;N;.

REVEL

Benign

0.020

Sift

Benign

0.43

T;T;.

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0060

B;B;.

Vest4

0.23

MVP

0.40

MPC

0.081

ClinPred

0.0048

GERP RS

3.7

Varity_R

0.026

gMVP

0.27

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