rs145965684

Variant names:

• chr9-127943224-C-G
• NM_001035254.3:c.1123G>C

Your query was ambiguous. Multiple possible variants found:

• chr9-127943224-C-G
• chr9-127943224-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001035254.3(EEIG1):​c.1123G>C​(p.Val375Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. V375I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: EEIG1 NM_001035254.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.46

Genes affected

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

ACMG classification

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=0.22553885).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EEIG1	NM_001035254.3	c.1123G>C	p.Val375Leu	missense_variant	Exon 11 of 11	ENST00000373095.6	NP_001030331.1
EEIG1	NM_203305.3	c.697G>C	p.Val233Leu	missense_variant	Exon 8 of 8		NP_976050.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EEIG1	ENST00000373095.6	c.1123G>C	p.Val375Leu	missense_variant	Exon 11 of 11	5	NM_001035254.3	ENSP00000362187.1
EEIG1	ENST00000373084.8	c.697G>C	p.Val233Leu	missense_variant	Exon 8 of 8	1		ENSP00000362176.4
EEIG1	ENST00000300434.3	n.807G>C		non_coding_transcript_exon_variant	Exon 6 of 6	1
EEIG1	ENST00000465821.5	n.1973G>C		non_coding_transcript_exon_variant	Exon 5 of 5	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461844 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727222

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.018	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.027	T;.
Eigen	Benign	-0.025
Eigen_PC	Benign	0.18
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.7	L;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.72	N;N
REVEL	Benign	0.26
Sift	Benign	0.037	D;D
Sift4G	Benign	0.27	T;T
Polyphen		0.0010	B;.
Vest4		0.31
MutPred		0.20		Loss of loop (P = 0.1242);.;
MVP		0.24
MPC		0.43
ClinPred		0.85	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.28
gMVP		0.29

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-130705503;