Genetic Variant GULP1:p.Pro17Ser (chr2-188483451-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_016315.4(GULP1):c.49C>T(p.Pro17Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000725 in 1,378,726 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

GULP1
NM_016315.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.76

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GULP1	NM_016315.4 link	c.49C>T	p.Pro17Ser	missense_variant	Exon 4 of 12	ENST00000409830.6	NP_057399.1	Q9UBP9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GULP1	ENST00000409830.6 link	c.49C>T	p.Pro17Ser	missense_variant	Exon 4 of 12	1	NM_016315.4	ENSP00000386732.1		Q9UBP9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.25e-7

AC:

AN:

1378726

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

689240

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000259

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.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 08, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.49C>T (p.P17S) alteration is located in exon 4 (coding exon 2) of the GULP1 gene. This alteration results from a C to T substitution at nucleotide position 49, causing the proline (P) at amino acid position 17 to be replaced by a serine (S). 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

Pathogenic

0.60

BayesDel_addAF

Uncertain

0.078

BayesDel_noAF

Benign

-0.13

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.31

.;T;.;.;.;T;T;.;T

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.94

D;.;.;D;D;.;.;D;D

M_CAP

Benign

0.020

MetaRNN

Uncertain

0.47

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.53

MutationAssessor

Uncertain

2.1

M;M;M;.;M;M;M;M;M

PrimateAI

Uncertain

0.77

PROVEAN

Pathogenic

-5.6

D;D;D;D;N;D;D;D;D

REVEL

Benign

0.18

Sift

Benign

0.042

D;D;D;D;D;D;D;D;D

Sift4G

Uncertain

0.044

D;D;T;T;T;D;D;T;D

Polyphen

0.0010, 0.98

.;B;D;.;.;B;B;D;B

Vest4

0.65

MutPred

0.47

Gain of MoRF binding (P = 0.0476);Gain of MoRF binding (P = 0.0476);Gain of MoRF binding (P = 0.0476);Gain of MoRF binding (P = 0.0476);Gain of MoRF binding (P = 0.0476);Gain of MoRF binding (P = 0.0476);Gain of MoRF binding (P = 0.0476);Gain of MoRF binding (P = 0.0476);Gain of MoRF binding (P = 0.0476);

MVP

0.37

MPC

0.18

ClinPred

0.98

GERP RS

5.8

Varity_R

0.50

gMVP

0.62

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over