9-127945397-C-A

Variant names:

• chr9-127945397-C-A
• rs529329211
• NM_001035254.3:c.887G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001035254.3(EEIG1):​c.887G>T​(p.Arg296Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000697 in 1,434,296 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R296W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: EEIG1 NM_001035254.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.83
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001035254.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EEIG1	NM_001035254.3	MANE Select	c.887G>T	p.Arg296Leu	missense	Exon 8 of 11	NP_001030331.1	Q5T9C2-1
	EEIG1	NM_203305.3		c.461G>T	p.Arg154Leu	missense	Exon 5 of 8	NP_976050.1	Q5T9C2-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EEIG1	ENST00000373095.6	TSL:5 MANE Select	c.887G>T	p.Arg296Leu	missense	Exon 8 of 11	ENSP00000362187.1	Q5T9C2-1
	EEIG1	ENST00000373084.8	TSL:1	c.461G>T	p.Arg154Leu	missense	Exon 5 of 8	ENSP00000362176.4	Q5T9C2-3
	EEIG1	ENST00000300434.3	TSL:1	n.571G>T		non_coding_transcript_exon	Exon 3 of 6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000505 AC: 1 AN: 198196 AF XY: 0.00

Gnomad AFR exome AF: 0.0000872

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 6.97e-7 AC: 1 AN: 1434296 Hom.: 0 Cov.: 33 AF XY: 0.00000141 AC XY: 1 AN XY: 710920

African (AFR) AF: 0.0000302 AC: 1 AN: 33086

American (AMR) AF: 0.00 AC: 0 AN: 41554

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25496

East Asian (EAS) AF: 0.00 AC: 0 AN: 38716

South Asian (SAS) AF: 0.00 AC: 0 AN: 82546

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50250

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4110

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1099404

Other (OTH) AF: 0.00 AC: 0 AN: 59134

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000839 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.033	T
Eigen	Benign	0.17
Eigen_PC	Benign	0.18
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		4.8
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.87	N
REVEL	Benign	0.18
Sift	Benign	0.26	T
Sift4G	Benign	0.58	T
Polyphen		0.83	P
Vest4		0.63
MutPred		0.32		Gain of catalytic residue at R296 (P = 0.0082)
MVP		0.42
MPC		0.56
ClinPred		0.66	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.16
gMVP		0.54
Mutation Taster		=52/48	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs529329211; hg19: chr9-130707676;