22-44497504-G-C

Variant names:

• chr22-44497504-G-C
• rs1448717946
• NM_032287.3:c.53C>G

Variant summary

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

The NM_032287.3(RTL6):​c.53C>G​(p.Pro18Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P18L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RTL6 NM_032287.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69
• Publications: 0 publications found

Genes affected

RTL6 (HGNC:13343): (retrotransposon Gag like 6)

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 (MetaRNN=0.061011642).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032287.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTL6	NM_032287.3	MANE Select	c.53C>G	p.Pro18Arg	missense	Exon 2 of 2	NP_115663.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTL6	ENST00000341255.4	TSL:1 MANE Select	c.53C>G	p.Pro18Arg	missense	Exon 2 of 2	ENSP00000340434.3	Q6ICC9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461816 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727206

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53362

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112002

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	18
DANN	Benign	0.93
DEOGEN2	Benign	0.026	T
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-0.98	T
PhyloP100		1.7
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.71	N
REVEL	Benign	0.023
Sift	Uncertain	0.012	D
Polyphen		0.0090	B
Vest4		0.029
MutPred		0.16		Loss of loop (P = 9e-04)
MVP		0.12
MPC		0.77
ClinPred		0.13	T
GERP RS		1.9
Varity_R		0.049
gMVP		0.57
Mutation Taster		=99/1	polymorphism

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: rs1448717946; hg19: chr22-44893384;