1-109619568-C-T

Position:

• chr1-109619568-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001377295.2(GNAT2):​c.-139G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0305 in 152,548 control chromosomes in the GnomAD database, including 105 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.031 (105 hom., cov: 33)
  • Exomes 𝑓: 0.012 (0 hom.)
• Consequence: GNAT2 NM_001377295.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.925

Genes affected

GNAT2 (HGNC:4394): (G protein subunit alpha transducin 2) Transducin is a 3-subunit guanine nucleotide-binding protein (G protein) which stimulates the coupling of rhodopsin and cGMP-phoshodiesterase during visual impulses. The transducin alpha subunits in rods and cones are encoded by separate genes. This gene encodes the alpha subunit in cones. [provided by RefSeq, Jul 2008]

AMPD2 (HGNC:469): (adenosine monophosphate deaminase 2) The protein encoded by this gene is important in purine metabolism by converting AMP to IMP. The encoded protein, which acts as a homotetramer, is one of three AMP deaminases found in mammals. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 1-109619568-C-T is Benign according to our data. Variant chr1-109619568-C-T is described in ClinVar as [Benign]. Clinvar id is 1246281.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNAT2	NM_001377295.2	c.-139G>A		5_prime_UTR_variant	1/9	ENST00000679935.1	NP_001364224.1
GNAT2	NM_001379232.1	c.-54+7G>A		splice_region_variant, intron_variant			NP_001366161.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNAT2	ENST00000679935.1	c.-139G>A		5_prime_UTR_variant	1/9		NM_001377295.2	ENSP00000505083	P1
AMPD2	ENST00000531734.6	c.-129-572C>T		intron_variant		4		ENSP00000433739
GNAT2	ENST00000622865.1	c.-54+320G>A		intron_variant		3		ENSP00000482596
AMPD2	ENST00000655992.1	c.-329C>T		5_prime_UTR_variant, NMD_transcript_variant	1/17			ENSP00000499740

Frequencies

GnomAD3 genomes AF: 0.0306 AC: 4656 AN: 152266 Hom.: 105 Cov.: 33

Gnomad AFR AF: 0.00805

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.0305

Gnomad ASJ AF: 0.0104

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00496

Gnomad FIN AF: 0.0248

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0503

Gnomad OTH AF: 0.0316

GnomAD4 exome AF: 0.0122 AC: 2 AN: 164 Hom.: 0 Cov.: 0 AF XY: 0.00862 AC XY: 1 AN XY: 116

Gnomad4 AMR exome AF: 0.500

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0625

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0305 AC: 4655 AN: 152384 Hom.: 105 Cov.: 33 AF XY: 0.0295 AC XY: 2200 AN XY: 74512

Gnomad4 AFR AF: 0.00803

Gnomad4 AMR AF: 0.0305

Gnomad4 ASJ AF: 0.0104

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00497

Gnomad4 FIN AF: 0.0248

Gnomad4 NFE AF: 0.0503

Gnomad4 OTH AF: 0.0313

Alfa AF: 0.0426 Hom.: 20

Bravo AF: 0.0299

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.9
DANN	Benign	0.78

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs56079255; hg19: chr1-110162190;