9-127945436-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001035254.3(EEIG1):​c.848G>A​(p.Arg283Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000014 in 1,566,288 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R283W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

EEIG1
NM_001035254.3 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.35
Variant links:
Genes affected
EEIG1 (HGNC:31419): (estrogen-induced osteoclastogenesis regulator 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.02605179).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EEIG1NM_001035254.3 linkc.848G>A p.Arg283Gln missense_variant Exon 8 of 11 ENST00000373095.6 NP_001030331.1 Q5T9C2-1
EEIG1NM_203305.3 linkc.422G>A p.Arg141Gln missense_variant Exon 5 of 8 NP_976050.1 Q5T9C2-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EEIG1ENST00000373095.6 linkc.848G>A p.Arg283Gln missense_variant Exon 8 of 11 5 NM_001035254.3 ENSP00000362187.1 Q5T9C2-1
EEIG1ENST00000373084.8 linkc.422G>A p.Arg141Gln missense_variant Exon 5 of 8 1 ENSP00000362176.4 Q5T9C2-3
EEIG1ENST00000300434.3 linkn.532G>A non_coding_transcript_exon_variant Exon 3 of 6 1
EEIG1ENST00000465821.5 linkn.321G>A non_coding_transcript_exon_variant Exon 3 of 5 2

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152240
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000116
AC:
2
AN:
171712
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
91984
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000740
Gnomad ASJ exome
AF:
0.00
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:
0.0000134
AC:
19
AN:
1413930
Hom.:
0
Cov.:
33
AF XY:
0.0000143
AC XY:
10
AN XY:
699260
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000783
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:
0.0000129
Gnomad4 OTH exome
AF:
0.0000171
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152358
Hom.:
0
Cov.:
32
AF XY:
0.0000268
AC XY:
2
AN XY:
74496
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000142
Hom.:
0
Bravo
AF:
0.0000264
ExAC
AF:
0.00000853
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 15, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.848G>A (p.R283Q) 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 848, causing the arginine (R) at amino acid position 283 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
0.076
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.59
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.020
T;.
Eigen
Benign
-0.25
Eigen_PC
Benign
-0.099
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Benign
0.79
T;T
M_CAP
Benign
0.0086
T
MetaRNN
Benign
0.026
T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Uncertain
2.0
M;.
PrimateAI
Uncertain
0.53
T
PROVEAN
Benign
-0.19
N;N
REVEL
Benign
0.13
Sift
Benign
0.27
T;T
Sift4G
Benign
0.37
T;T
Polyphen
0.82
P;.
Vest4
0.13
MVP
0.34
MPC
0.47
ClinPred
0.26
T
GERP RS
4.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.092
gMVP
0.18

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.

Other links and lift over

dbSNP: rs200989232; hg19: chr9-130707715; COSMIC: COSV55947376; COSMIC: COSV55947376; API