9-127945690-G-A

Variant names:

• chr9-127945690-G-A
• rs1350462462
• NM_001035254.3:c.680C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001035254.3(EEIG1):​c.680C>T​(p.Ser227Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000694 in 1,440,704 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: 6.9e-7 (0 hom.)
• Consequence: EEIG1 NM_001035254.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.45
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29705268).

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.680C>T	p.Ser227Phe	missense	Exon 7 of 11	NP_001030331.1	Q5T9C2-1
	EEIG1	NM_203305.3		c.254C>T	p.Ser85Phe	missense	Exon 4 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.680C>T	p.Ser227Phe	missense	Exon 7 of 11	ENSP00000362187.1	Q5T9C2-1
	EEIG1	ENST00000373084.8	TSL:1	c.254C>T	p.Ser85Phe	missense	Exon 4 of 8	ENSP00000362176.4	Q5T9C2-3
	EEIG1	ENST00000300434.3	TSL:1	n.364C>T		non_coding_transcript_exon	Exon 2 of 6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.94e-7 AC: 1 AN: 1440704 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 714710

African (AFR) AF: 0.00 AC: 0 AN: 33024

American (AMR) AF: 0.00 AC: 0 AN: 41504

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25670

East Asian (EAS) AF: 0.00 AC: 0 AN: 38464

South Asian (SAS) AF: 0.00 AC: 0 AN: 82722

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51540

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5602

European-Non Finnish (NFE) AF: 9.07e-7 AC: 1 AN: 1102658

Other (OTH) AF: 0.00 AC: 0 AN: 59520

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	Uncertain	0.46
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.30	T
Eigen	Benign	0.14
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		6.5
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Benign	0.20
Sift	Uncertain	0.027	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.012	B
Vest4		0.49
MutPred		0.23		Loss of phosphorylation at S227 (P = 0.0176)
MVP		0.37
MPC		0.42
ClinPred		0.99	D
GERP RS		4.9
Varity_R		0.67
gMVP		0.69
Mutation Taster		=39/61	disease causing

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

Other links and lift over

dbSNP: rs1350462462; hg19: chr9-130707969;