19-49426788-A-G

Position:

• chr19-49426788-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001195256.2(GFY):​c.358A>G​(p.Met120Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000217 in 1,383,988 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: GFY NM_001195256.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.372

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.057098985).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GFY	NM_001195256.2	c.358A>G	p.Met120Val	missense_variant	2/4	ENST00000610896.3
GFY	NM_001385187.1	c.358A>G	p.Met120Val	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GFY	ENST00000610896.3	c.358A>G	p.Met120Val	missense_variant	2/4	2	NM_001195256.2	P1
GFY	ENST00000576655.5	c.358A>G	p.Met120Val	missense_variant	3/5	5		P1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000217 AC: 3 AN: 1383988 Hom.: 0 Cov.: 31 AF XY: 0.00000146 AC XY: 1 AN XY: 682924

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: 0.00000185

Gnomad4 OTH exome AF: 0.0000173

GnomAD4 genome Cov.: 30

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

Mar 20, 2023

The c.358A>G (p.M120V) 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 358, causing the methionine (M) at amino acid position 120 to be replaced by a valine (V). 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	0.083
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	4.5
DANN	Benign	0.72
DEOGEN2	Benign	0.0013	T;T
FATHMM_MKL	Benign	0.13	N
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.057	T;T
MutationAssessor	Benign	0.0	N;N
Sift4G	Benign	1.0	T;T
Vest4		0.029
MVP		0.21
GERP RS		4.6
Varity_R		0.30
gMVP		0.15

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: chr19-49930045;