chr2-188529184-C-T

Variant names:

• chr2-188529184-C-T
• rs376744592
• NM_016315.4:c.250C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_016315.4(GULP1):​c.250C>T​(p.Pro84Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000147 in 1,356,666 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: GULP1 NM_016315.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.57
• Publications: 0 publications found

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]

ACMG classification

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=0.34721452).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GULP1	NM_016315.4	MANE Select	c.250C>T	p.Pro84Ser	missense	Exon 6 of 12	NP_057399.1	Q9UBP9-1
	GULP1	NM_001375948.1		c.250C>T	p.Pro84Ser	missense	Exon 6 of 13	NP_001362877.1	H7BZV7
	GULP1	NM_001375949.1		c.250C>T	p.Pro84Ser	missense	Exon 7 of 14	NP_001362878.1	H7BZV7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GULP1	ENST00000409830.6	TSL:1 MANE Select	c.250C>T	p.Pro84Ser	missense	Exon 6 of 12	ENSP00000386732.1	Q9UBP9-1
	GULP1	ENST00000359135.7	TSL:1	c.250C>T	p.Pro84Ser	missense	Exon 6 of 12	ENSP00000352047.3	Q9UBP9-1
	GULP1	ENST00000410051.5	TSL:1	c.250C>T	p.Pro84Ser	missense	Exon 6 of 7	ENSP00000387013.1	Q9UBP9-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000147 AC: 2 AN: 1356666 Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0 AN XY: 679024

African (AFR) AF: 0.00 AC: 0 AN: 30492

American (AMR) AF: 0.00 AC: 0 AN: 39768

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25016

East Asian (EAS) AF: 0.00 AC: 0 AN: 38686

South Asian (SAS) AF: 0.00 AC: 0 AN: 79078

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53190

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5556

European-Non Finnish (NFE) AF: 0.00000195 AC: 2 AN: 1028154

Other (OTH) AF: 0.00 AC: 0 AN: 56726

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.039	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.54	T
MutationAssessor	Benign	1.6	L
PhyloP100		7.6
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.19
Sift	Benign	0.22	T
Sift4G	Benign	0.16	T
Polyphen		0.10	B
Vest4		0.55
MutPred		0.32		Loss of glycosylation at P84 (P = 0.0543)
MVP		0.35
MPC		0.22
ClinPred		0.95	D
GERP RS		5.5
Varity_R		0.32
gMVP		0.58
Mutation Taster		=29/71	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs376744592; hg19: chr2-189393911;