Genetic Variant EEIG1:p.Arg296Gln (chr9-127945397-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001035254.3(EEIG1):c.887G>A(p.Arg296Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000101 in 1,586,572 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000056 ( 0 hom. )

Consequence

EEIG1
NM_001035254.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.83

Variant links:

Genes affected

EEIG1 (HGNC:31419): (estrogen-induced osteoclastogenesis regulator 1)

EEIG1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13777646).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EEIG1	NM_001035254.3 link	c.887G>A	p.Arg296Gln	missense_variant	Exon 8 of 11	ENST00000373095.6	NP_001030331.1	Q5T9C2-1
EEIG1	NM_203305.3 link	c.461G>A	p.Arg154Gln	missense_variant	Exon 5 of 8		NP_976050.1	Q5T9C2-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
EEIG1	ENST00000373095.6 link	c.887G>A	p.Arg296Gln	missense_variant	Exon 8 of 11	5	NM_001035254.3	ENSP00000362187.1	Q5T9C2-1
EEIG1	ENST00000373084.8 link	c.461G>A	p.Arg154Gln	missense_variant	Exon 5 of 8	1		ENSP00000362176.4	Q5T9C2-3
EEIG1	ENST00000300434.3 link	n.571G>A		non_coding_transcript_exon_variant	Exon 3 of 6	1
EEIG1	ENST00000465821.5 link	n.360G>A		non_coding_transcript_exon_variant	Exon 3 of 5	2

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000151

AC:

AN:

198196

Hom.:

AF XY:

0.0000186

AC XY:

AN XY:

107268

show subpopulations

Gnomad AFR exome

AF:

0.000174

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000113

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000558

AC:

AN:

1434296

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

710920

show subpopulations

Gnomad4 AFR exome

AF:

0.000121

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000273

Gnomad4 OTH exome

AF:

0.0000169

GnomAD4 genome

AF:

0.0000525

AC:

AN:

152276

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000302

ExAC

AF:

0.0000168

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.887G>A (p.R296Q) alteration is located in exon 8 (coding exon 8) of the FAM102A gene. This alteration results from a G to A substitution at nucleotide position 887, causing the arginine (R) at amino acid position 296 to be replaced by a glutamine (Q). 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

Benign

0.12

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.043

T;.

Eigen

Benign

0.16

Eigen_PC

Benign

0.17

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.88

D;D

M_CAP

Benign

0.018

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

M;.

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.64

N;N

REVEL

Benign

0.11

Sift

Benign

0.44

T;T

Sift4G

Benign

0.57

T;T

Polyphen

0.95

P;.

Vest4

0.39

MutPred

0.24

Loss of MoRF binding (P = 0.0455);.;

MVP

0.42

MPC

0.87

ClinPred

0.80

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.072

gMVP

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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