Variant 1-169851914-A-C 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.2342A>C(p.Glu781Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00116 in 1,614,086 control chromosomes in the GnomAD database, including 19 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 Benign (★).

Frequency

Genomes: 𝑓 0.0019 ( 6 hom., cov: 31)

Exomes 𝑓: 0.0011 ( 13 hom. )

Consequence

FIRRM
NM_001320047.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.14

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=0.0033718944).

BP6

Variant 1-169851914-A-C is Benign according to our data. Variant chr1-169851914-A-C is described in ClinVar as [Benign]. Clinvar id is 711777.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FIRRM	NM_001320047.2 linkuse as main transcript	c.2342A>C	p.Glu781Ala	missense_variant	24/25	ENST00000359326.9	NP_001306976.1	Q9NSG2-1A0A024R922
SCYL3	NM_020423.7 linkuse as main transcript	c.*1799T>G		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.2342A>C	p.Glu781Ala	missense_variant	24/25	1	NM_001320047.2	ENSP00000352276.4		Q9NSG2-1
SCYL3	ENST00000367771 linkuse as main transcript	c.*1799T>G		3_prime_UTR_variant	13/13	1	NM_020423.7	ENSP00000356745.5		Q8IZE3-2

Frequencies

GnomAD3 genomes

AF:

0.00190

AC:

289

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00212

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.0334

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000955

Gnomad OTH

AF:

0.00334

GnomAD3 exomes

AF:

0.00185

AC:

465

AN:

251180

Hom.:

AF XY:

0.00179

AC XY:

243

AN XY:

135750

show subpopulations

Gnomad AFR exome

AF:

0.00178

Gnomad AMR exome

AF:

0.000955

Gnomad ASJ exome

AF:

0.0305

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000713

Gnomad OTH exome

AF:

0.00245

GnomAD4 exome

AF:

0.00109

AC:

1589

AN:

1461742

Hom.:

Cov.:

AF XY:

0.00108

AC XY:

786

AN XY:

727174

show subpopulations

Gnomad4 AFR exome

AF:

0.00251

Gnomad4 AMR exome

AF:

0.000894

Gnomad4 ASJ exome

AF:

0.0280

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000487

Gnomad4 OTH exome

AF:

0.00305

GnomAD4 genome

AF:

0.00190

AC:

289

AN:

152344

Hom.:

Cov.:

AF XY:

0.00166

AC XY:

124

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.00212

Gnomad4 AMR

AF:

0.000849

Gnomad4 ASJ

AF:

0.0334

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000956

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00213

Hom.:

Bravo

AF:

0.00193

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.00233

AC:

ExAC

AF:

0.00143

AC:

174

EpiCase

AF:

0.000818

EpiControl

AF:

0.00107

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.0090

DANN

Benign

0.71

DEOGEN2

Benign

0.019

T;T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.059

LIST_S2

Benign

0.64

.;T;T

M_CAP

Benign

0.0038

MetaRNN

Benign

0.0034

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.75

N;N;.

PROVEAN

Benign

-1.4

N;N;.

REVEL

Benign

0.0040

Sift

Benign

0.46

T;T;.

Sift4G

Benign

0.41

T;T;T

Polyphen

0.0010

B;B;.

Vest4

0.16

MVP

0.12

MPC

0.065

ClinPred

0.00095

GERP RS

-3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.032

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

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