1-108612187-G-T

Variant names:

• chr1-108612187-G-T
• rs1444990985
• NM_001010883.3:c.298G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001010883.3(EEIG2):​c.298G>T​(p.Ala100Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,458,902 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. A100T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: EEIG2 NM_001010883.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.09
• Publications: 0 publications found

Genes affected

EEIG2 (HGNC:27637): (EEIG family member 2)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.768

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EEIG2	NM_001010883.3	c.298G>T	p.Ala100Ser	missense_variant	Exon 4 of 11	ENST00000370035.8	NP_001010883.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EEIG2	ENST00000370035.8	c.298G>T	p.Ala100Ser	missense_variant	Exon 4 of 11	1	NM_001010883.3	ENSP00000359052.3
EEIG2	ENST00000405454.1	c.298G>T	p.Ala100Ser	missense_variant	Exon 4 of 11	5		ENSP00000386084.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000401 AC: 1 AN: 249302 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: 6.85e-7 AC: 1 AN: 1458902 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 725876

African (AFR) AF: 0.00 AC: 0 AN: 33332

American (AMR) AF: 0.00 AC: 0 AN: 44036

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26056

East Asian (EAS) AF: 0.00 AC: 0 AN: 39634

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53372

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110644

Other (OTH) AF: 0.00 AC: 0 AN: 60268

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Uncertain	0.050	T
BayesDel_noAF	Uncertain	-0.060
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T;.
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D;D
M_CAP	Benign	0.012	T
MetaRNN	Pathogenic	0.77	D;D
MetaSVM	Benign	-0.79	T
MutationAssessor	Uncertain	2.7	M;M
PhyloP100		8.1
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-1.5	N;N
REVEL	Uncertain	0.30
Sift	Uncertain	0.010	D;D
Sift4G	Uncertain	0.060	T;T
Polyphen		0.98	D;.
Vest4		0.77
MutPred		0.66		Gain of ubiquitination at K96 (P = 0.07);Gain of ubiquitination at K96 (P = 0.07);
MVP		0.69
MPC		0.84
ClinPred		0.83	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.34
gMVP		0.67
Mutation Taster		=64/36	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: rs1444990985; hg19: chr1-109154809;