2-188541236-C-G

Variant names:

• chr2-188541236-C-G
• NM_016315.4:c.317C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_016315.4(GULP1):​c.317C>G​(p.Thr106Ser) 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 benign 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: 7.84

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35648656).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GULP1	NM_016315.4	c.317C>G	p.Thr106Ser	missense_variant	Exon 7 of 12	ENST00000409830.6	NP_057399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GULP1	ENST00000409830.6	c.317C>G	p.Thr106Ser	missense_variant	Exon 7 of 12	1	NM_016315.4	ENSP00000386732.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 16, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.317C>G (p.T106S) alteration is located in exon 7 (coding exon 5) of the GULP1 gene. This alteration results from a C to G substitution at nucleotide position 317, causing the threonine (T) at amino acid position 106 to be replaced by a serine (S). 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	Uncertain	0.36
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.038	.;T;.;T;T;.;T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.88	D;.;.;.;.;D;D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.36	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.41	N;N;N;N;N;N;N
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.59	N;N;N;N;N;N;N
REVEL	Benign	0.13
Sift	Benign	0.70	T;T;T;T;T;T;T
Sift4G	Benign	0.85	T;T;T;T;T;T;T
Polyphen		1.0, 1.0	.;D;D;D;D;D;D
Vest4		0.68
MutPred		0.30		Gain of disorder (P = 0.0453);Gain of disorder (P = 0.0453);Gain of disorder (P = 0.0453);Gain of disorder (P = 0.0453);Gain of disorder (P = 0.0453);Gain of disorder (P = 0.0453);Gain of disorder (P = 0.0453);
MVP		0.34
MPC		0.66
ClinPred		0.93	D
GERP RS		5.5
Varity_R		0.48
gMVP		0.21

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.

Other links and lift over

hg19: chr2-189405963;