Genetic Variant EEIG1:p.Pro292Leu (chr9-127945409-G-A) – 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.875C>T(p.Pro292Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000024 in 1,581,364 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 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

EEIG1
NM_001035254.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.08

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=0.18590751).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EEIG1	NM_001035254.3 link	c.875C>T	p.Pro292Leu	missense_variant	Exon 8 of 11	ENST00000373095.6	NP_001030331.1	Q5T9C2-1
EEIG1	NM_203305.3 link	c.449C>T	p.Pro150Leu	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.875C>T	p.Pro292Leu	missense_variant	Exon 8 of 11	5	NM_001035254.3	ENSP00000362187.1	Q5T9C2-1
EEIG1	ENST00000373084.8 link	c.449C>T	p.Pro150Leu	missense_variant	Exon 5 of 8	1		ENSP00000362176.4	Q5T9C2-3
EEIG1	ENST00000300434.3 link	n.559C>T		non_coding_transcript_exon_variant	Exon 3 of 6	1
EEIG1	ENST00000465821.5 link	n.348C>T		non_coding_transcript_exon_variant	Exon 3 of 5	2

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152200

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000262

AC:

AN:

190554

Hom.:

AF XY:

0.0000291

AC XY:

AN XY:

102934

show subpopulations

Gnomad AFR exome

AF:

0.0000910

Gnomad AMR exome

AF:

0.0000676

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000133

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:

0.0000217

AC:

AN:

1429164

Hom.:

Cov.:

AF XY:

0.0000198

AC XY:

AN XY:

707898

show subpopulations

Gnomad4 AFR exome

AF:

0.0000909

Gnomad4 AMR exome

AF:

0.0000490

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000260

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000228

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.000145

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000529

ESP6500AA

AF:

0.000460

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000338

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 15, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.875C>T (p.P292L) alteration is located in exon 8 (coding exon 8) of the FAM102A gene. This alteration results from a C to T substitution at nucleotide position 875, causing the proline (P) at amino acid position 292 to be replaced by a leucine (L). 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

0.079

BayesDel_addAF

Benign

-0.057

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Benign

0.96

DEOGEN2

Benign

0.075

T;.

Eigen

Benign

0.066

Eigen_PC

Benign

-0.080

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.84

T;D

M_CAP

Benign

0.030

MetaRNN

Benign

0.19

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

M;.

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-2.2

N;N

REVEL

Benign

0.26

Sift

Benign

0.16

T;T

Sift4G

Benign

0.17

T;T

Polyphen

1.0

D;.

Vest4

0.43

MVP

0.47

MPC

0.48

ClinPred

0.25

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.075

gMVP

0.35

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.

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