Variant 2-188587876-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_016315.4(GULP1):c.770A>T(p.Glu257Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000689 in 1,450,426 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.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

GULP1
NM_016315.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.99

Variant links:

Genes affected

GULP1 (HGNC:18649): (GULP PTB domain containing engulfment adaptor 1) The protein encoded by this gene is an adapter protein necessary for the engulfment of apoptotic cells by phagocytes. Several transcript variants, some protein coding and some thought not to be protein coding, have been found for this gene. [provided by RefSeq, Nov 2011]

GULP1 links:

GULP1 (HGNC:):

GULP1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.38542438).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GULP1	NM_016315.4 linkuse as main transcript	c.770A>T	p.Glu257Val	missense_variant	11/12	ENST00000409830.6	NP_057399.1	Q9UBP9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GULP1	ENST00000409830.6 linkuse as main transcript	c.770A>T	p.Glu257Val	missense_variant	11/12	1	NM_016315.4	ENSP00000386732.1		Q9UBP9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.89e-7

AC:

AN:

1450426

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722298

show subpopulations

Gnomad4 AFR exome

AF:

0.0000301

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.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 10, 2024

The c.770A>T (p.E257V) alteration is located in exon 11 (coding exon 9) of the GULP1 gene. This alteration results from a A to T substitution at nucleotide position 770, causing the glutamic acid (E) at amino acid position 257 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Pathogenic

0.29

BayesDel_noAF

Pathogenic

0.18

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.24

.;T;.;T;T;T

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.92

D;.;D;.;.;D

M_CAP

Benign

0.056

MetaRNN

Benign

0.39

T;T;T;T;T;T

MetaSVM

Benign

-0.77

MutationAssessor

Benign

0.63

N;N;.;N;N;N

PrimateAI

Uncertain

0.77

PROVEAN

Uncertain

-2.6

D;D;N;D;D;D

REVEL

Uncertain

0.41

Sift

Benign

0.21

T;T;T;T;T;T

Sift4G

Uncertain

0.050

T;T;T;T;T;T

Polyphen

0.028

.;B;.;B;B;B

Vest4

0.61

MutPred

0.34

Loss of solvent accessibility (P = 0.0199);Loss of solvent accessibility (P = 0.0199);.;Loss of solvent accessibility (P = 0.0199);Loss of solvent accessibility (P = 0.0199);Loss of solvent accessibility (P = 0.0199);

MVP

0.65

MPC

0.22

ClinPred

0.92

GERP RS

5.4

Varity_R

0.23

gMVP

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over