Genetic Variant NM_016315.4:c.256A>G (chr2-188529190-A-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_016315.4(GULP1):c.256A>G(p.Thr86Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000153 in 1,311,444 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

GULP1
NM_016315.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.67

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.256A>G	p.Thr86Ala	missense	Exon 6 of 12	NP_057399.1	Q9UBP9-1
GULP1	NM_001375948.1		c.256A>G	p.Thr86Ala	missense	Exon 6 of 13	NP_001362877.1	H7BZV7
GULP1	NM_001375949.1		c.256A>G	p.Thr86Ala	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.256A>G	p.Thr86Ala	missense	Exon 6 of 12	ENSP00000386732.1	Q9UBP9-1
GULP1	ENST00000359135.7	TSL:1	c.256A>G	p.Thr86Ala	missense	Exon 6 of 12	ENSP00000352047.3	Q9UBP9-1
GULP1	ENST00000410051.5	TSL:1	c.256A>G	p.Thr86Ala	missense	Exon 6 of 7	ENSP00000387013.1	Q9UBP9-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000437

AC:

AN:

228868

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000355

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:

0.0000153

AC:

AN:

1311444

Hom.:

Cov.:

AF XY:

0.0000152

AC XY:

AN XY:

659006

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29492

American (AMR)

AF:

0.0000260

AC:

AN:

38522

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24556

East Asian (EAS)

AF:

0.00

AC:

AN:

38708

South Asian (SAS)

AF:

0.00

AC:

AN:

78110

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53194

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5438

European-Non Finnish (NFE)

AF:

0.0000182

AC:

AN:

988214

Other (OTH)

AF:

0.0000181

AC:

AN:

55210

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

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:

0.0000113

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Uncertain

-0.010

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.048

MetaRNN

Uncertain

0.50

MetaSVM

Uncertain

-0.0022

MutationAssessor

Pathogenic

3.5

PhyloP100

5.7

PrimateAI

Uncertain

0.69

PROVEAN

Uncertain

-3.6

REVEL

Uncertain

0.37

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.0090

Polyphen

0.35

Vest4

0.62

MutPred

0.69

Loss of sheet (P = 0.0817)

MVP

0.62

MPC

0.36

ClinPred

0.95

GERP RS

5.5

Varity_R

0.55

gMVP

0.55

Mutation Taster

=14/86

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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