Variant 2-188584340-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_016315.4(GULP1):c.685T>C(p.Ser229Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,453,590 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

GULP1
NM_016315.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.942

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06349176).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GULP1	NM_016315.4 linkuse as main transcript	c.685T>C	p.Ser229Pro	missense_variant	10/12	ENST00000409830.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GULP1	ENST00000409830.6 linkuse as main transcript	c.685T>C	p.Ser229Pro	missense_variant	10/12	1	NM_016315.4	P1	Q9UBP9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1453590

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723804

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000505

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 22, 2023

The c.685T>C (p.S229P) alteration is located in exon 10 (coding exon 8) of the GULP1 gene. This alteration results from a T to C substitution at nucleotide position 685, causing the serine (S) at amino acid position 229 to be replaced by a proline (P). 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

0.056

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.98

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.72

T;.;T;.;.;T

M_CAP

Benign

0.0062

MetaRNN

Benign

0.063

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

L;L;.;L;L;L

MutationTaster

Benign

0.53

D;D;D;D;D;D

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.71

N;N;N;N;N;N

REVEL

Benign

0.10

Sift

Benign

0.070

T;T;D;T;T;T

Sift4G

Benign

0.33

T;T;T;T;T;T

Polyphen

0.0

.;B;.;B;B;B

Vest4

0.20

MutPred

0.14

Gain of relative solvent accessibility (P = 0.0249);Gain of relative solvent accessibility (P = 0.0249);.;Gain of relative solvent accessibility (P = 0.0249);Gain of relative solvent accessibility (P = 0.0249);Gain of relative solvent accessibility (P = 0.0249);

MVP

0.25

MPC

0.23

ClinPred

0.21

GERP RS

-1.1

Varity_R

0.096

gMVP

0.28

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