ECRG4 p.Thr47Ser

Variant names:

• chr2-106073897-A-T
• NM_032411.3:c.139A>T
• ECRG4 p.Thr47Ser

Your query was ambiguous. Multiple possible variants found:

• chr2-106073897-A-T
• chr2-106073898-C-G
• chr2-106073897-ACT-TCC
• chr2-106073897-ACT-TCA
• chr2-106073897-ACT-TCG
• chr2-106073898-CT-GC

Variant summary

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

The NM_032411.3(ECRG4):​c.139A>T​(p.Thr47Ser) 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. 14/23 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ECRG4 NM_032411.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.10
• Publications: 0 publications found

Genes affected

ECRG4 (HGNC:24642): (ECRG4 augurin precursor) Enables neuropeptide hormone activity. Involved in neuropeptide signaling pathway; positive regulation of hormone secretion; and vasopressin secretion. Located in apical plasma membrane; dense core granule; and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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_032411.3. 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
	ECRG4	NM_032411.3	MANE Select	c.139A>T	p.Thr47Ser	missense	Exon 3 of 4	NP_115787.1	Q9H1Z8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ECRG4	ENST00000238044.8	TSL:1 MANE Select	c.139A>T	p.Thr47Ser	missense	Exon 3 of 4	ENSP00000238044.3	Q9H1Z8
	ECRG4	ENST00000437659.1	TSL:3	c.145A>T	p.Thr49Ser	missense	Exon 4 of 5	ENSP00000388664.1	C9JRR0
	ECRG4	ENST00000409944.5	TSL:5	c.31A>T	p.Thr11Ser	missense	Exon 4 of 5	ENSP00000386421.1	B8ZZE5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.0010
DANN	Benign	0.75
DEOGEN2	Benign	0.0035	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.022	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PhyloP100		-3.1
PROVEAN	Benign	-0.18	N
REVEL	Benign	0.031
Sift	Benign	0.83	T
Sift4G	Benign	0.89	T
Varity_R		0.033
gMVP		0.15
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.29		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.29		Position offset: 6

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr2-106690353;