17-46978975-C-T

Variant names:

• chr17-46978975-C-T
• NM_203400.5:c.33G>A
• RPRML p.Leu11Leu

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_203400.5(RPRML):​c.33G>A​(p.Leu11Leu) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RPRML NM_203400.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.403
• Publications: 0 publications found

Genes affected

RPRML (HGNC:32422): (reprimo like) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000262633 (HGNC:):

LRRC37A2 (HGNC:32404): (leucine rich repeat containing 37 member A2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP7: Synonymous conserved (PhyloP=0.403 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203400.5. 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
	RPRML	NM_203400.5	MANE Select	c.33G>A	p.Leu11Leu	synonymous	Exon 1 of 1	NP_981945.1	Q8N4K4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPRML	ENST00000322329.5	TSL:6 MANE Select	c.33G>A	p.Leu11Leu	synonymous	Exon 1 of 1	ENSP00000318032.3	Q8N4K4
	ENSG00000262633	ENST00000571841.1	TSL:5	n.676+12349C>T		intron	N/A	ENSP00000461460.1	E7EQ34
	ENSG00000291209	ENST00000570478.6	TSL:4	n.291+204C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1296828 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 639210

African (AFR) AF: 0.00 AC: 0 AN: 25184

American (AMR) AF: 0.00 AC: 0 AN: 19502

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21792

East Asian (EAS) AF: 0.00 AC: 0 AN: 28044

South Asian (SAS) AF: 0.00 AC: 0 AN: 68964

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32846

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3986

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1042962

Other (OTH) AF: 0.00 AC: 0 AN: 53548

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	16
DANN	Benign	0.97
PhyloP100		0.40
PromoterAI		-0.029	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr17-45056341;