NM_024627.6:c.*1392C>T

Variant names:

• chr22-19849775-G-A
• rs10372
• NM_024627.6:c.*1392C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RTL10	NM_024627.6	c.*1392C>T		3_prime_UTR_variant	Exon 3 of 3	ENST00000328554.9	NP_078903.3
GNB1L	NM_053004.3	c.-21+4668C>T		intron_variant	Intron 2 of 7	ENST00000329517.11	NP_443730.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RTL10	ENST00000328554.9	c.*1392C>T		3_prime_UTR_variant	Exon 3 of 3	1	NM_024627.6	ENSP00000330596.4
GNB1L	ENST00000329517.11	c.-21+4668C>T		intron_variant	Intron 2 of 7	1	NM_053004.3	ENSP00000331313.6

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

African (AFR) AF: 0.365 AC: 5763 AN: 15778

American (AMR) AF: 0.113 AC: 111 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 1016 AN: 5144

East Asian (EAS) AF: 0.0267 AC: 97 AN: 3628

South Asian (SAS) AF: 0.200 AC: 3298 AN: 16456

European-Finnish (FIN) AF: 0.0899 AC: 25 AN: 278

Middle Eastern (MID) AF: 0.188 AC: 305 AN: 1620

European-Non Finnish (NFE) AF: 0.128 AC: 97473 AN: 761434

Other (OTH) AF: 0.148 AC: 4026 AN: 27288

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

African (AFR) AF: 0.348 AC: 14430 AN: 41450

American (AMR) AF: 0.133 AC: 2035 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 730 AN: 3468

East Asian (EAS) AF: 0.0324 AC: 168 AN: 5186

South Asian (SAS) AF: 0.187 AC: 903 AN: 4828

European-Finnish (FIN) AF: 0.0929 AC: 985 AN: 10604

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9672 AN: 68010

Other (OTH) AF: 0.181 AC: 384 AN: 2116

Alfa AF: 0.182 Hom.: 489

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
PhyloP100		-0.092
Mutation Taster		=100/0	polymorphism (auto)

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: rs10372; hg19: chr22-19837298;