chr22-44497412-C-G

Variant names:

• chr22-44497412-C-G
• NM_032287.3:c.145G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032287.3(RTL6):​c.145G>C​(p.Glu49Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: RTL6 NM_032287.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.16
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16455022).

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.145G>C	p.Glu49Gln	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.145G>C	p.Glu49Gln	missense	Exon 2 of 2	ENSP00000340434.3	Q6ICC9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.036	T
Eigen	Benign	0.051
Eigen_PC	Benign	0.067
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
PhyloP100		1.2
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	0.52	N
REVEL	Benign	0.091
Sift	Benign	0.66	T
Polyphen		0.97	D
Vest4		0.12
MutPred		0.28		Gain of MoRF binding (P = 0.0241)
MVP		0.31
MPC		1.6
ClinPred		0.88	D
GERP RS		3.1
Varity_R		0.11
gMVP		0.54
Mutation Taster		=92/8	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

hg19: chr22-44893292;