chr9-77648184-G-T

Variant names:

• chr9-77648184-G-T
• rs1122838
• NM_004297.4:c.-391C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004297.4(GNA14):​c.-391C>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 0.0000139 in 143,570 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 0.000014 (0 hom.)
• Consequence: GNA14 NM_004297.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.41
• Publications: 0 publications found

Genes affected

GNA14 (HGNC:4382): (G protein subunit alpha 14) This gene encodes a member of the guanine nucleotide-binding, or G protein family. G proteins are heterotrimers consisting of alpha, beta and gamma subunits. The encoded protein is a member of the alpha family of G proteins, more specifically the alpha q subfamily of G proteins. The encoded protein may play a role in pertussis-toxin resistant activation of phospholipase C-beta and its downstream effectors.[provided by RefSeq, Feb 2009]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004297.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNA14	NM_004297.4	MANE Select	c.-391C>A		5_prime_UTR	Exon 1 of 7	NP_004288.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNA14	ENST00000341700.7	TSL:1 MANE Select	c.-391C>A		5_prime_UTR	Exon 1 of 7	ENSP00000365807.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000139 AC: 2 AN: 143570 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 76582

African (AFR) AF: 0.00 AC: 0 AN: 1818

American (AMR) AF: 0.00 AC: 0 AN: 3156

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3696

East Asian (EAS) AF: 0.00 AC: 0 AN: 3072

South Asian (SAS) AF: 0.00 AC: 0 AN: 25330

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8910

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 582

European-Non Finnish (NFE) AF: 0.0000224 AC: 2 AN: 89154

Other (OTH) AF: 0.00 AC: 0 AN: 7852

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.78
DANN	Benign	0.72
PhyloP100		-2.4
PromoterAI		-0.022	Neutral

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

Other links and lift over

dbSNP: rs1122838; hg19: chr9-80263100;