rs6624595

Variant names:

• chrX-72130283-T-A
• rs6624595
• ENST00000609883.3:c.1258A>T

Your query was ambiguous. Multiple possible variants found:

• chrX-72130283-T-A
• chrX-72130283-T-C
• chrX-72130283-T-G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000609883.3(RTL5):​c.1258A>T​(p.Ser420Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000184 in 1,197,154 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/17 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. S420R) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.000028 (0 hom., 1 hem., cov: 21)
  • Exomes 𝑓: 0.000017 (0 hom. 9 hem.)
• Consequence: RTL5 ENST00000609883.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.153
• Publications: 15 publications found

Genes affected

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

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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04168448).
• BS2: High Hemizygotes in GnomAdExome4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NHSL2	NM_001013627.3	c.281-1796T>A		intron_variant	Intron 1 of 7	ENST00000633930.2	NP_001013649.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RTL5	ENST00000609883.3	c.1258A>T	p.Ser420Cys	missense_variant	Exon 1 of 1	6		ENSP00000476792.1
NHSL2	ENST00000633930.2	c.281-1796T>A		intron_variant	Intron 1 of 7	5	NM_001013627.3	ENSP00000488668.1

Frequencies

GnomAD3 genomes AF: 0.0000276 AC: 3 AN: 108539 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00125

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000389 AC: 7 AN: 180056 AF XY: 0.0000605

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000745

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000175 AC: 19 AN: 1088558 Hom.: 0 Cov.: 32 AF XY: 0.0000254 AC XY: 9 AN XY: 354382

African (AFR) AF: 0.00 AC: 0 AN: 26203

American (AMR) AF: 0.00 AC: 0 AN: 35075

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19306

East Asian (EAS) AF: 0.000133 AC: 4 AN: 30163

South Asian (SAS) AF: 0.000204 AC: 11 AN: 53898

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40467

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4117

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 833557

Other (OTH) AF: 0.0000874 AC: 4 AN: 45772

GnomAD4 genome AF: 0.0000276 AC: 3 AN: 108596 Hom.: 0 Cov.: 21 AF XY: 0.0000322 AC XY: 1 AN XY: 31012

African (AFR) AF: 0.00 AC: 0 AN: 29808

American (AMR) AF: 0.00 AC: 0 AN: 10178

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2602

East Asian (EAS) AF: 0.00 AC: 0 AN: 3359

South Asian (SAS) AF: 0.00126 AC: 3 AN: 2390

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5638

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 214

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52249

Other (OTH) AF: 0.00 AC: 0 AN: 1486

Alfa AF: 0.00 Hom.: 7523

Bravo AF: 0.00000756

ExAC AF: 0.0000248 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.6
DANN	Benign	0.87
DEOGEN2	Benign	0.0012	T
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.15
PrimateAI	Benign	0.29	T
Sift4G	Uncertain	0.0020	D
Polyphen		0.93	P
Vest4		0.049
MutPred		0.20		Loss of phosphorylation at S420 (P = 3e-04);
MVP		0.014
ClinPred		0.039	T
GERP RS		1.3
Varity_R		0.069
gMVP		0.029
Mutation Taster		=100/0	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: rs6624595; hg19: chrX-71350133;