Genetic Variant ENST00000609883.3:c.1637G>A (chrX-72129904-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The ENST00000609883.3(RTL5):c.1637G>A(p.Arg546His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,096,876 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 0.000011 ( 0 hom. 2 hem. )

Consequence

RTL5
ENST00000609883.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0770

Publications

2 publications found

Variant links:

Genes affected

RTL5 (HGNC:29430): (retrotransposon Gag like 5)

RTL5 links:

NHSL2 (HGNC:33737): (NHS like 2) Predicted to enable calcium ion binding activity. Predicted to be involved in cell differentiation. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

NHSL2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09946433).

BS2

High Hemizygotes in GnomAdExome4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000609883.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RTL5	NM_001405151.1	MANE Select	c.1637G>A	p.Arg546His	missense	Exon 1 of 1	NP_001392080.1	Q5HYW3
NHSL2	NM_001013627.3	MANE Select	c.281-2175C>T		intron	N/A	NP_001013649.2	Q5HYW2-1
RTL5	NM_001024455.4		c.1637G>A	p.Arg546His	missense	Exon 1 of 2	NP_001019626.1	Q5HYW3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RTL5	ENST00000609883.3	TSL:6 MANE Select	c.1637G>A	p.Arg546His	missense	Exon 1 of 1	ENSP00000476792.1	Q5HYW3
NHSL2	ENST00000633930.2	TSL:5 MANE Select	c.281-2175C>T		intron	N/A	ENSP00000488668.1	Q5HYW2-1
RTL5	ENST00000479991.1	TSL:1	n.1637G>A		non_coding_transcript_exon	Exon 1 of 2	ENSP00000418667.1	Q5HYW3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000223

AC:

AN:

179244

AF XY:

0.0000153

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000734

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000250

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000109

AC:

AN:

1096876

Hom.:

Cov.:

AF XY:

0.00000552

AC XY:

AN XY:

362368

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26395

American (AMR)

AF:

0.0000853

AC:

AN:

35166

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19315

East Asian (EAS)

AF:

0.00

AC:

AN:

30203

South Asian (SAS)

AF:

0.00

AC:

AN:

53979

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40453

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4131

European-Non Finnish (NFE)

AF:

0.00000951

AC:

AN:

841196

Other (OTH)

AF:

0.0000217

AC:

AN:

46038

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000936

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000579

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0033

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.59

M_CAP

Benign

0.0044

MetaRNN

Benign

0.099

MetaSVM

Benign

-1.0

PhyloP100

-0.077

PrimateAI

Uncertain

0.58

Sift4G

Uncertain

0.060

Polyphen

0.99

Vest4

0.23

MutPred

0.30

Loss of glycosylation at P547 (P = 0.0655)

MVP

0.17

ClinPred

0.14

GERP RS

3.1

Varity_R

0.070

gMVP

0.096

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over