chr2-188541286-C-T

Variant names:

• chr2-188541286-C-T
• NM_016315.4:c.367C>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_016315.4(GULP1):​c.367C>T​(p.His123Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GULP1 NM_016315.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.82
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.806

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.367C>T	p.His123Tyr	missense	Exon 7 of 12	NP_057399.1	Q9UBP9-1
	GULP1	NM_001375948.1		c.367C>T	p.His123Tyr	missense	Exon 7 of 13	NP_001362877.1	H7BZV7
	GULP1	NM_001375949.1		c.367C>T	p.His123Tyr	missense	Exon 8 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.367C>T	p.His123Tyr	missense	Exon 7 of 12	ENSP00000386732.1	Q9UBP9-1
	GULP1	ENST00000359135.7	TSL:1	c.367C>T	p.His123Tyr	missense	Exon 7 of 12	ENSP00000352047.3	Q9UBP9-1
	GULP1	ENST00000410051.5	TSL:1	c.367C>T	p.His123Tyr	missense	Exon 7 of 7	ENSP00000387013.1	Q9UBP9-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

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	Pathogenic	0.92
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.27
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Pathogenic	0.87
Eigen_PC	Pathogenic	0.87
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.041	D
MetaRNN	Pathogenic	0.81	D
MetaSVM	Uncertain	-0.19	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		7.8
PrimateAI	Pathogenic	0.88	D
PROVEAN	Pathogenic	-5.1	D
REVEL	Uncertain	0.60
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.96
MutPred		0.60		Loss of catalytic residue at H123 (P = 0.0801)
MVP		0.72
MPC		0.72
ClinPred		0.99	D
GERP RS		5.7
Varity_R		0.95
gMVP		0.63
Mutation Taster		=7/93	disease causing

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

Other links and lift over

hg19: chr2-189406013; COSMIC: COSV63064589;