Variant 19-49427098-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001195256.2(GFY):c.668A>G(p.Glu223Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000456 in 1,535,506 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 9/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0000043 ( 0 hom. )

Consequence

GFY
NM_001195256.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.315

Variant links:

Genes affected

GFY (HGNC:44663): (golgi associated olfactory signaling regulator) Predicted to be involved in sensory perception of smell. Predicted to act upstream of or within non-motile cilium assembly and protein localization to non-motile cilium. Predicted to be located in Golgi apparatus. Predicted to be integral component of Golgi membrane. [provided by Alliance of Genome Resources, Apr 2022]

GFY links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.0855788).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GFY	NM_001195256.2 linkuse as main transcript	c.668A>G	p.Glu223Gly	missense_variant	2/4	ENST00000610896.3
GFY	NM_001385187.1 linkuse as main transcript	c.668A>G	p.Glu223Gly	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GFY	ENST00000610896.3 linkuse as main transcript	c.668A>G	p.Glu223Gly	missense_variant	2/4	2	NM_001195256.2	P1
GFY	ENST00000576655.5 linkuse as main transcript	c.668A>G	p.Glu223Gly	missense_variant	3/5	5		P1

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151676

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000743

AC:

AN:

134648

Hom.:

AF XY:

0.0000136

AC XY:

AN XY:

73312

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000189

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000434

AC:

AN:

1383830

Hom.:

Cov.:

AF XY:

0.00000586

AC XY:

AN XY:

682860

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000463

Gnomad4 OTH exome

AF:

0.0000173

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151676

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74024

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000575

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 29, 2022

The c.668A>G (p.E223G) alteration is located in exon 1 (coding exon 1) of the GFY gene. This alteration results from a A to G substitution at nucleotide position 668, causing the glutamic acid (E) at amino acid position 223 to be replaced by a glycine (G). 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

0.099

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0058

T;T

FATHMM_MKL

Benign

0.049

M_CAP

Benign

0.018

MetaRNN

Benign

0.086

T;T

MutationAssessor

Benign

0.34

N;N

Sift4G

Benign

0.26

T;T

Vest4

0.064

MVP

0.32

GERP RS

-0.75

Varity_R

0.057

gMVP

0.36

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over