dbSNP rs376744592: GULP1:p.Pro84Thr (chr2-188529184-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_016315.4(GULP1):c.250C>A(p.Pro84Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000147 in 1,356,664 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P84S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

GULP1
NM_016315.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.57

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.37094352).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016315.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GULP1	NM_016315.4	MANE Select	c.250C>A	p.Pro84Thr	missense	Exon 6 of 12	NP_057399.1	Q9UBP9-1
GULP1	NM_001375948.1		c.250C>A	p.Pro84Thr	missense	Exon 6 of 13	NP_001362877.1	H7BZV7
GULP1	NM_001375949.1		c.250C>A	p.Pro84Thr	missense	Exon 7 of 14	NP_001362878.1	H7BZV7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GULP1	ENST00000409830.6	TSL:1 MANE Select	c.250C>A	p.Pro84Thr	missense	Exon 6 of 12	ENSP00000386732.1	Q9UBP9-1
GULP1	ENST00000359135.7	TSL:1	c.250C>A	p.Pro84Thr	missense	Exon 6 of 12	ENSP00000352047.3	Q9UBP9-1
GULP1	ENST00000410051.5	TSL:1	c.250C>A	p.Pro84Thr	missense	Exon 6 of 7	ENSP00000387013.1	Q9UBP9-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000865

AC:

AN:

231326

AF XY:

0.00000798

show subpopulations

Gnomad AFR exome

AF:

0.0000662

Gnomad AMR exome

AF:

0.0000339

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000147

AC:

AN:

1356664

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

679022

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

30492

American (AMR)

AF:

0.00

AC:

AN:

39766

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25016

East Asian (EAS)

AF:

0.00

AC:

AN:

38686

South Asian (SAS)

AF:

0.00

AC:

AN:

79078

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53190

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5556

European-Non Finnish (NFE)

AF:

9.73e-7

AC:

AN:

1028154

Other (OTH)

AF:

0.0000176

AC:

AN:

56726

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Uncertain

0.067

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.16

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.018

MetaRNN

Benign

0.37

MetaSVM

Benign

-0.66

MutationAssessor

Benign

0.79

PhyloP100

7.6

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-3.7

REVEL

Benign

0.17

Sift

Benign

0.18

Sift4G

Benign

0.32

Polyphen

0.81

Vest4

0.60

MVP

0.33

MPC

0.46

ClinPred

0.90

GERP RS

5.5

Varity_R

0.52

gMVP

0.59

Mutation Taster

=36/64

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over