chr9-127944655-C-T

Variant names:

• chr9-127944655-C-T
• rs1461397159
• NM_001035254.3:c.1069G>A

Variant summary

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

The NM_001035254.3(EEIG1):​c.1069G>A​(p.Asp357Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,460,284 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: EEIG1 NM_001035254.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.20
• 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.1069G>A	p.Asp357Asn	missense	Exon 10 of 11	NP_001030331.1	Q5T9C2-1
	EEIG1	NM_203305.3		c.643G>A	p.Asp215Asn	missense	Exon 7 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.1069G>A	p.Asp357Asn	missense	Exon 10 of 11	ENSP00000362187.1	Q5T9C2-1
	EEIG1	ENST00000373084.8	TSL:1	c.643G>A	p.Asp215Asn	missense	Exon 7 of 8	ENSP00000362176.4	Q5T9C2-3
	EEIG1	ENST00000300434.3	TSL:1	n.753G>A		non_coding_transcript_exon	Exon 5 of 6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 249134 AF XY: 0.00

Gnomad AFR exome AF: 0.00

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: 0.00000342 AC: 5 AN: 1460284 Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3 AN XY: 726490

African (AFR) AF: 0.00 AC: 0 AN: 33458

American (AMR) AF: 0.00 AC: 0 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86222

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5310

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111866

Other (OTH) AF: 0.0000166 AC: 1 AN: 60312

GnomAD4 genome Cov.: 33

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	0.29
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.65	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		7.2
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.21
Sift	Benign	0.16	T
Sift4G	Benign	0.10	T
Polyphen		1.0	D
Vest4		0.75
MutPred		0.38		Gain of MoRF binding (P = 0.0453)
MVP		0.49
MPC		1.2
ClinPred		0.90	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.75
Mutation Taster		=53/47	polymorphism

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: rs1461397159; hg19: chr9-130706934; COSMIC: COSV100305529; COSMIC: COSV100305529;