14-92931498-G-T

Variant names:

• chr14-92931498-G-T
• NM_001275.4:c.604G>T

Variant summary

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

The NM_001275.4(CHGA):​c.604G>T​(p.Asp202Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,356 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CHGA NM_001275.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.238

Genes affected

CHGA (HGNC:1929): (chromogranin A) The protein encoded by this gene is a member of the chromogranin/secretogranin family of neuroendocrine secretory proteins. It is found in secretory vesicles of neurons and endocrine cells. This gene product is a precursor to three biologically active peptides; vasostatin, pancreastatin, and parastatin. These peptides act as autocrine or paracrine negative modulators of the neuroendocrine system. Two other peptides, catestatin and chromofungin, have antimicrobial activity and antifungal activity, respectively. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 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=0.2597081).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHGA	NM_001275.4	c.604G>T	p.Asp202Tyr	missense_variant	Exon 6 of 8	ENST00000216492.10	NP_001266.1
CHGA	XM_011536370.3	c.604G>T	p.Asp202Tyr	missense_variant	Exon 7 of 9		XP_011534672.1
CHGA	NM_001301690.2	c.356-872G>T		intron_variant	Intron 5 of 6		NP_001288619.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHGA	ENST00000216492.10	c.604G>T	p.Asp202Tyr	missense_variant	Exon 6 of 8	1	NM_001275.4	ENSP00000216492.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460356 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726326

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T
Eigen	Benign	0.0075
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.12	N
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.075
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.0070	D
Polyphen		1.0	D
Vest4		0.39
MutPred		0.41		Gain of phosphorylation at D202 (P = 0.0073);
MVP		0.32
MPC		0.85
ClinPred		0.76	D
GERP RS		4.0
Varity_R		0.17
gMVP		0.31

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-93397843;