X-112454900-C-T

Variant names:

• chrX-112454900-C-T
• rs183504232
• NM_001395362.2:c.172C>T

Variant summary

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

The NM_001395362.2(RTL4):​c.172C>T​(p.Leu58Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000447 in 1,208,699 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 13 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00023 (0 hom., 6 hem., cov: 23)
  • Exomes 𝑓: 0.000026 (0 hom. 7 hem.)
• Consequence: RTL4 NM_001395362.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.232
• Publications: 0 publications found

Genes affected

RTL4 (HGNC:25214): (retrotransposon Gag like 4) Predicted to enable nucleic acid binding activity and zinc ion binding activity. Predicted to act upstream of or within cognition and norepinephrine metabolic process. [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=0.018987656).
• BS2: High Hemizygotes in GnomAd4 at 6 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395362.2. 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
	RTL4	NM_001395362.2	MANE Select	c.172C>T	p.Leu58Phe	missense	Exon 5 of 5	NP_001382291.1	Q6ZR62
	RTL4	NM_001004308.3		c.172C>T	p.Leu58Phe	missense	Exon 3 of 3	NP_001004308.2	Q6ZR62

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTL4	ENST00000695839.1	MANE Select	c.172C>T	p.Leu58Phe	missense	Exon 5 of 5	ENSP00000512211.1	Q6ZR62
	RTL4	ENST00000340433.4	TSL:6	c.172C>T	p.Leu58Phe	missense	Exon 4 of 4	ENSP00000340590.2	Q6ZR62
	RTL4	ENST00000695808.1		c.172C>T	p.Leu58Phe	missense	Exon 3 of 3	ENSP00000512188.1	Q6ZR62

Frequencies

GnomAD3 genomes AF: 0.000233 AC: 26 AN: 111522 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000978

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00199

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00134

GnomAD2 exomes AF: 0.0000165 AC: 3 AN: 181668 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000732

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000223

GnomAD4 exome AF: 0.0000255 AC: 28 AN: 1097124 Hom.: 0 Cov.: 34 AF XY: 0.0000193 AC XY: 7 AN XY: 362558

African (AFR) AF: 0.000114 AC: 3 AN: 26393

American (AMR) AF: 0.000427 AC: 15 AN: 35159

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19316

East Asian (EAS) AF: 0.00 AC: 0 AN: 30146

South Asian (SAS) AF: 0.00 AC: 0 AN: 53938

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40490

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4125

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841506

Other (OTH) AF: 0.000217 AC: 10 AN: 46051

GnomAD4 genome AF: 0.000233 AC: 26 AN: 111575 Hom.: 0 Cov.: 23 AF XY: 0.000178 AC XY: 6 AN XY: 33753

African (AFR) AF: 0.0000976 AC: 3 AN: 30737

American (AMR) AF: 0.00199 AC: 21 AN: 10546

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2652

East Asian (EAS) AF: 0.00 AC: 0 AN: 3517

South Asian (SAS) AF: 0.00 AC: 0 AN: 2554

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6061

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 215

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53089

Other (OTH) AF: 0.00132 AC: 2 AN: 1516

Alfa AF: 0.000136 Hom.: 0

Bravo AF: 0.000533

ExAC AF: 0.00000824 AC: 1

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	Benign	0.089
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.74
DANN	Benign	0.85
DEOGEN2	Benign	0.094	T
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.019	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.23
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.011
Sift	Benign	0.14	T
Sift4G	Benign	0.21	T
Polyphen		0.015	B
Vest4		0.059
MVP		0.16
MPC		0.014
ClinPred		0.020	T
GERP RS		-1.8
PromoterAI		0.020	Neutral
Varity_R		0.10
gMVP		0.095
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: rs183504232; hg19: chrX-111698128;