19-56177158-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033106.4(GALP):c.50G>T(p.Ser17Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: GALP NM_033106.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.640

Genes affected

GALP (HGNC:24840): (galanin like peptide) This gene encodes a member of the galanin family of neuropeptides. The encoded protein binds galanin receptors 1, 2 and 3 with the highest affinity for galanin receptor 3 and has been implicated in biological processes involving the central nervous system including hypothalamic regulation of metabolism and reproduction. A peptide encoded by a splice variant of this gene, termed alarin, has vasoactive properties, displays antimicrobial activity against E. coli, and may serve as a marker for neuroblastic tumors.[provided by RefSeq, Nov 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11961335).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GALP	NM_033106.4	c.50G>T	p.Ser17Ile	missense_variant	2/6	ENST00000357330.7
GALP	NM_001145546.2	c.50G>T	p.Ser17Ile	missense_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GALP	ENST00000357330.7	c.50G>T	p.Ser17Ile	missense_variant	2/6	1	NM_033106.4	P2
GALP	ENST00000590002.1	c.50G>T	p.Ser17Ile	missense_variant	1/2	1		A2
GALP	ENST00000440823.1	c.50G>T	p.Ser17Ile	missense_variant	2/5	5		A2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 17, 2023

The c.50G>T (p.S17I) alteration is located in exon 2 (coding exon 1) of the GALP gene. This alteration results from a G to T substitution at nucleotide position 50, causing the serine (S) at amino acid position 17 to be replaced by an isoleucine (I). 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	Benign	0.20
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
Cadd	Benign	13
Dann	Benign	0.80
DEOGEN2	Benign	0.39	T;.;.
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.29	T;T;.
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N;N;N
MutationTaster	Benign	0.93	N;N;N
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-2.5	N;D;.
REVEL	Benign	0.034
Sift	Pathogenic	0.0	D;.;.
Sift4G	Benign	0.24	T;D;D
Polyphen		0.028	B;B;B
Vest4		0.32
MutPred		0.39		Loss of disorder (P = 0.0191);Loss of disorder (P = 0.0191);Loss of disorder (P = 0.0191);
MVP		0.21
MPC		0.12
ClinPred		0.26	T
GERP RS		1.3
Varity_R		0.34
gMVP		0.29

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: chr19-56688527;