1-108624685-T-A

Variant names:

• chr1-108624685-T-A
• rs1427953447
• NM_001010883.3:c.493T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001010883.3(EEIG2):​c.493T>A​(p.Ser165Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict 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. S165P) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: EEIG2 NM_001010883.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.961
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.042897135).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010883.3. 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
	EEIG2	NM_001010883.3	MANE Select	c.493T>A	p.Ser165Thr	missense	Exon 6 of 11	NP_001010883.2	Q5T8I3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EEIG2	ENST00000370035.8	TSL:1 MANE Select	c.493T>A	p.Ser165Thr	missense	Exon 6 of 11	ENSP00000359052.3	Q5T8I3-1
	EEIG2	ENST00000931507.1		c.493T>A	p.Ser165Thr	missense	Exon 6 of 11	ENSP00000601566.1
	EEIG2	ENST00000931506.1		c.493T>A	p.Ser165Thr	missense	Exon 6 of 11	ENSP00000601565.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152168 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152168 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74344

African (AFR) AF: 0.00 AC: 0 AN: 41436

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	16
DANN	Benign	0.90
DEOGEN2	Benign	0.027	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.27
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.043	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.96
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.37	N
REVEL	Benign	0.014
Sift	Benign	0.53	T
Sift4G	Benign	0.49	T
Polyphen		0.0080	B
Vest4		0.11
MutPred		0.18		Gain of helix (P = 0.132)
MVP		0.36
MPC		0.38
ClinPred		0.21	T
GERP RS		3.2
Varity_R		0.054
gMVP		0.20
Mutation Taster		=89/11	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: rs1427953447; hg19: chr1-109167307;