22-44497349-T-A

Variant names:

• chr22-44497349-T-A
• NM_032287.3:c.208A>T

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.208A>T​(p.Arg70Trp) 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. 12/21 in silico tools predict 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: -0.517
• 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=0.16653848).

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.208A>T	p.Arg70Trp	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.208A>T	p.Arg70Trp	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	Pathogenic	0.64
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.058	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.090	N
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.98	T
PhyloP100		-0.52
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.14
Sift	Benign	0.053	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.53	P
Vest4		0.25
MutPred		0.39		Loss of disorder (P = 0.0023)
MVP		0.30
MPC		1.8
ClinPred		0.46	T
GERP RS		-3.0
Varity_R		0.053
gMVP		0.60
Mutation Taster		=82/18	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: chr22-44893229;