dbSNP rs139780486: GET4:p.Leu151Val (chr7-887504-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015949.3(GET4):c.451C>G(p.Leu151Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000717 in 1,395,540 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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. L151F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

GET4
NM_015949.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.81

Variant links:

Genes affected

GET4 (HGNC:21690): (guided entry of tail-anchored proteins factor 4) Enables chaperone binding activity. Involved in cytoplasmic sequestering of protein; maintenance of unfolded protein involved in ERAD pathway; and tail-anchored membrane protein insertion into ER membrane. Located in chromosome; cytosol; and nuclear lumen. Part of BAT3 complex. [provided by Alliance of Genome Resources, Apr 2022]

GET4 links:

SUN1 (HGNC:18587): (Sad1 and UNC84 domain containing 1) This gene is a member of the unc-84 homolog family and encodes a nuclear envelope protein with an Unc84 (SUN) domain. The protein is involved in nuclear anchorage and migration. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jan 2019]

SUN1 links:

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ACMG classification

Classification made for transcript

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=0.17815202).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GET4	NM_015949.3 link	c.451C>G	p.Leu151Val	missense_variant	Exon 4 of 9	ENST00000265857.8	NP_057033.2	Q7L5D6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GET4	ENST00000265857.8 link	c.451C>G	p.Leu151Val	missense_variant	Exon 4 of 9	1	NM_015949.3	ENSP00000265857.3		Q7L5D6-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000508

AC:

AN:

196898

Hom.:

AF XY:

0.00000944

AC XY:

AN XY:

105962

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000218

GnomAD4 exome

AF:

7.17e-7

AC:

AN:

1395540

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

688998

show subpopulations

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000240

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.074

T;T;.;T;.

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.074

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.84

T;D;T;T;T

M_CAP

Benign

0.0063

MetaRNN

Benign

0.18

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

L;.;.;.;.

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-0.93

N;.;N;N;N

REVEL

Benign

0.022

Sift

Benign

0.61

T;.;T;T;T

Sift4G

Benign

0.33

T;T;T;T;T

Polyphen

0.0020

B;.;.;.;.

Vest4

0.16

MutPred

0.34

Loss of stability (P = 0.0895);.;.;.;.;

MVP

0.12

MPC

0.21

ClinPred

0.17

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.092

gMVP

0.10

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over