9-127945478-C-G

Variant names:

• chr9-127945478-C-G
• NM_001035254.3:c.806G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001035254.3(EEIG1):​c.806G>C​(p.Gly269Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000212 in 1,414,054 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: EEIG1 NM_001035254.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.92
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17507777).

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.806G>C	p.Gly269Ala	missense	Exon 8 of 11	NP_001030331.1	Q5T9C2-1
	EEIG1	NM_203305.3		c.380G>C	p.Gly127Ala	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.806G>C	p.Gly269Ala	missense	Exon 8 of 11	ENSP00000362187.1	Q5T9C2-1
	EEIG1	ENST00000373084.8	TSL:1	c.380G>C	p.Gly127Ala	missense	Exon 5 of 8	ENSP00000362176.4	Q5T9C2-3
	EEIG1	ENST00000300434.3	TSL:1	n.490G>C		non_coding_transcript_exon	Exon 3 of 6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000212 AC: 3 AN: 1414054 Hom.: 0 Cov.: 33 AF XY: 0.00000143 AC XY: 1 AN XY: 699518

African (AFR) AF: 0.00 AC: 0 AN: 32434

American (AMR) AF: 0.00 AC: 0 AN: 38242

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25358

East Asian (EAS) AF: 0.00 AC: 0 AN: 37038

South Asian (SAS) AF: 0.00 AC: 0 AN: 80716

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49114

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4198

European-Non Finnish (NFE) AF: 0.00000276 AC: 3 AN: 1088580

Other (OTH) AF: 0.00 AC: 0 AN: 58374

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.089
Eigen_PC	Benign	0.016
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		3.9
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.94	N
REVEL	Benign	0.084
Sift	Benign	0.21	T
Sift4G	Benign	0.15	T
Polyphen		0.022	B
Vest4		0.18
MutPred		0.33		Loss of glycosylation at S268 (P = 0.062)
MVP		0.39
MPC		0.64
ClinPred		0.48	T
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.35
Mutation Taster		=65/35	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

hg19: chr9-130707757;