chr22-19849775-G-A

Position:

• chr22-19849775-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024627.6(RTL10):​c.*1392C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 984,764 control chromosomes in the GnomAD database, including 11,735 homozygotes. 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: 𝑓 0.19 (3648 hom., cov: 33)
  • Exomes 𝑓: 0.13 (8087 hom.)
• Consequence: RTL10 NM_024627.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0920

Genes affected

RTL10 (HGNC:26112): (retrotransposon Gag like 10) Involved in mitochondrial outer membrane permeabilization and regulation of mitochondrial membrane potential. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

GNB1L (HGNC:4397): (G protein subunit beta 1 like) This gene encodes a G-protein beta-subunit-like polypeptide which is a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. This protein contains 6 WD repeats and is highly expressed in the heart. The gene maps to the region on chromosome 22q11, which is deleted in DiGeorge syndrome, trisomic in derivative 22 syndrome and tetrasomic in cat-eye syndrome. Therefore, this gene may contribute to the etiology of those disorders. Transcripts from this gene share exons with some transcripts from the C22orf29 gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RTL10	NM_024627.6	c.*1392C>T		3_prime_UTR_variant	3/3	ENST00000328554.9	NP_078903.3
GNB1L	NM_053004.3	c.-21+4668C>T		intron_variant		ENST00000329517.11	NP_443730.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RTL10	ENST00000328554.9	c.*1392C>T		3_prime_UTR_variant	3/3	1	NM_024627.6	ENSP00000330596	P1
GNB1L	ENST00000329517.11	c.-21+4668C>T		intron_variant		1	NM_053004.3	ENSP00000331313	P1

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29463 AN: 152036 Hom.: 3627 Cov.: 33

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.0323

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.0929

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.180

GnomAD4 exome AF: 0.135 AC: 112114 AN: 832610 Hom.: 8087 Cov.: 29 AF XY: 0.135 AC XY: 51738 AN XY: 384518

Gnomad4 AFR exome AF: 0.365

Gnomad4 AMR exome AF: 0.113

Gnomad4 ASJ exome AF: 0.198

Gnomad4 EAS exome AF: 0.0267

Gnomad4 SAS exome AF: 0.200

Gnomad4 FIN exome AF: 0.0899

Gnomad4 NFE exome AF: 0.128

Gnomad4 OTH exome AF: 0.148

GnomAD4 genome AF: 0.194 AC: 29536 AN: 152154 Hom.: 3648 Cov.: 33 AF XY: 0.191 AC XY: 14192 AN XY: 74382

Gnomad4 AFR AF: 0.348

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.210

Gnomad4 EAS AF: 0.0324

Gnomad4 SAS AF: 0.187

Gnomad4 FIN AF: 0.0929

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.181

Alfa AF: 0.176 Hom.: 444

Bravo AF: 0.200

Asia WGS AF: 0.134 AC: 466 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.9
DANN	Benign	0.63

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

Other links and lift over

dbSNP: rs10372; hg19: chr22-19837298;