rs750552945

Variant names:

• chr14-100880789-C-A
• rs750552945
• NM_001134888.3:c.4000G>T

Your query was ambiguous. Multiple possible variants found:

• chr14-100880789-C-A
• chr14-100880789-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001134888.3(RTL1):​c.4000G>T​(p.Ala1334Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000358 in 1,398,332 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000036 (0 hom.)
• Consequence: RTL1 NM_001134888.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.63

Genes affected

RTL1 (HGNC:14665): (retrotransposon Gag like 1) This gene is a retrotransposon-derived, paternally expressed imprinted gene that is highly expressed at the late fetal stage in both the fetus and placenta. It has an overlapping maternally expressed antisense transcript, which contains several microRNAs targeting the transcripts of this gene through an RNA interference (RNAi) mechanism. This gene is essential for maintenance of the fetal capillaries. [provided by RefSeq, Jul 2009]

MIR493HG (HGNC:55978): (MIR493 cluster host gene)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07544908).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RTL1	NM_001134888.3	c.4000G>T	p.Ala1334Ser	missense_variant	Exon 4 of 4	ENST00000649591.1	NP_001128360.1
RTL1	NM_001425285.1	c.4000G>T	p.Ala1334Ser	missense_variant	Exon 3 of 3		NP_001412214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RTL1	ENST00000649591.1	c.4000G>T	p.Ala1334Ser	missense_variant	Exon 4 of 4		NM_001134888.3	ENSP00000497482.1
MIR493HG	ENST00000637474.1	n.109-8860C>A		intron_variant	Intron 2 of 18	5

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000358 AC: 5 AN: 1398332 Hom.: 0 Cov.: 43 AF XY: 0.00000580 AC XY: 4 AN XY: 689702

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000463

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.0080
DANN	Benign	0.94
DEOGEN2	Benign	0.038	T;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.29	.;T
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.075	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;N
PrimateAI	Benign	0.42	T
PROVEAN	Benign	0.14	.;N
REVEL	Benign	0.010
Sift	Benign	0.037	.;D
Sift4G	Benign	0.11	.;T
Vest4		0.052
MutPred		0.22		Gain of catalytic residue at L1330 (P = 0);Gain of catalytic residue at L1330 (P = 0);
MVP		0.048
MPC		0.54
ClinPred		0.085	T
GERP RS		-2.7
Varity_R		0.046
gMVP		0.078

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

LitVar

Other links and lift over

dbSNP: rs750552945; hg19: chr14-101347126;