9-127943218-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001035254.3(EEIG1):​c.1129G>A​(p.Glu377Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000805 in 1,614,050 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

EEIG1
NM_001035254.3 missense

Scores

2
9
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.14
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 Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EEIG1NM_001035254.3 linkc.1129G>A p.Glu377Lys missense_variant Exon 11 of 11 ENST00000373095.6 NP_001030331.1 Q5T9C2-1
EEIG1NM_203305.3 linkc.703G>A p.Glu235Lys missense_variant Exon 8 of 8 NP_976050.1 Q5T9C2-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EEIG1ENST00000373095.6 linkc.1129G>A p.Glu377Lys missense_variant Exon 11 of 11 5 NM_001035254.3 ENSP00000362187.1 Q5T9C2-1
EEIG1ENST00000373084.8 linkc.703G>A p.Glu235Lys missense_variant Exon 8 of 8 1 ENSP00000362176.4 Q5T9C2-3
EEIG1ENST00000300434.3 linkn.813G>A non_coding_transcript_exon_variant Exon 6 of 6 1
EEIG1ENST00000465821.5 linkn.1979G>A non_coding_transcript_exon_variant Exon 5 of 5 2

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152198
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.0000159
AC:
4
AN:
251442
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135904
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000116
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:
0.00000752
AC:
11
AN:
1461852
Hom.:
0
Cov.:
30
AF XY:
0.00000550
AC XY:
4
AN XY:
727222
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.000134
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:
0.00000360
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152198
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74354
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
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
Bravo
AF:
0.0000378

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 22, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1129G>A (p.E377K) alteration is located in exon 11 (coding exon 11) of the FAM102A gene. This alteration results from a G to A substitution at nucleotide position 1129, causing the glutamic acid (E) at amino acid position 377 to be replaced by a lysine (K). 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
0.27
BayesDel_addAF
Uncertain
0.11
D
BayesDel_noAF
Uncertain
0.12
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.032
T;.
Eigen
Uncertain
0.42
Eigen_PC
Uncertain
0.51
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.97
D;D
M_CAP
Benign
0.0080
T
MetaRNN
Uncertain
0.45
T;T
MetaSVM
Benign
-0.86
T
MutationAssessor
Uncertain
2.1
M;.
PrimateAI
Pathogenic
0.80
T
PROVEAN
Benign
-1.1
N;N
REVEL
Uncertain
0.55
Sift
Benign
0.10
T;D
Sift4G
Benign
0.29
T;D
Polyphen
0.98
D;.
Vest4
0.66
MutPred
0.34
Gain of methylation at E377 (P = 0.0013);.;
MVP
0.41
MPC
1.3
ClinPred
0.79
D
GERP RS
5.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.39
gMVP
0.64

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: rs1300937255; hg19: chr9-130705497; API