9-127944843-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001035254.3(EEIG1):​c.973G>A​(p.Asp325Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,244 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

EEIG1
NM_001035254.3 missense

Scores

1
9
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.87
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 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.824

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EEIG1NM_001035254.3 linkc.973G>A p.Asp325Asn missense_variant Exon 9 of 11 ENST00000373095.6 NP_001030331.1 Q5T9C2-1
EEIG1NM_203305.3 linkc.547G>A p.Asp183Asn missense_variant Exon 6 of 8 NP_976050.1 Q5T9C2-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EEIG1ENST00000373095.6 linkc.973G>A p.Asp325Asn missense_variant Exon 9 of 11 5 NM_001035254.3 ENSP00000362187.1 Q5T9C2-1
EEIG1ENST00000373084.8 linkc.547G>A p.Asp183Asn missense_variant Exon 6 of 8 1 ENSP00000362176.4 Q5T9C2-3
EEIG1ENST00000300434.3 linkn.657G>A non_coding_transcript_exon_variant Exon 4 of 6 1
EEIG1ENST00000465821.5 linkn.446G>A non_coding_transcript_exon_variant Exon 4 of 5 2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000401
AC:
1
AN:
249432
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135228
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
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:
0.00000205
AC:
3
AN:
1460244
Hom.:
0
Cov.:
35
AF XY:
0.00
AC XY:
0
AN XY:
726518
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 16, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.973G>A (p.D325N) alteration is located in exon 9 (coding exon 9) of the FAM102A gene. This alteration results from a G to A substitution at nucleotide position 973, causing the aspartic acid (D) at amino acid position 325 to be replaced by an asparagine (N). 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
0.25
BayesDel_addAF
Benign
-0.079
T
BayesDel_noAF
Benign
-0.27
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.084
T;.
Eigen
Uncertain
0.52
Eigen_PC
Uncertain
0.44
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.94
D;D
M_CAP
Benign
0.078
D
MetaRNN
Pathogenic
0.82
D;D
MetaSVM
Uncertain
0.0087
D
MutationAssessor
Uncertain
2.2
M;.
PrimateAI
Uncertain
0.74
T
PROVEAN
Benign
-1.8
N;N
REVEL
Uncertain
0.40
Sift
Benign
0.19
T;T
Sift4G
Benign
0.43
T;T
Polyphen
1.0
D;.
Vest4
0.74
MutPred
0.68
Loss of disorder (P = 0.0946);.;
MVP
0.87
MPC
1.2
ClinPred
0.81
D
GERP RS
5.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.079
gMVP
0.59

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: rs761146464; hg19: chr9-130707122; COSMIC: COSV100305655; COSMIC: COSV100305655; API