rs6059655

Variant names:

• chr20-34077942-A-G
• rs6059655
• NM_016732.3:c.877-563A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016732.3(RALY):​c.877-563A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.956 in 152,348 control chromosomes in the GnomAD database, including 69,662 homozygotes. 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: 𝑓 0.96 (69662 hom., cov: 34)
• Consequence: RALY NM_016732.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.473
• Publications: 60 publications found

Genes affected

RALY (HGNC:15921): (RALY heterogeneous nuclear ribonucleoprotein) This gene encodes a member of the heterogeneous nuclear ribonucleoprotein (hnRNP) gene family. This protein may play a role in pre-mRNA splicing and in embryonic development. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RALY	NM_016732.3	c.877-563A>G		intron_variant	Intron 8 of 9	ENST00000246194.8	NP_057951.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RALY	ENST00000246194.8	c.877-563A>G		intron_variant	Intron 8 of 9	1	NM_016732.3	ENSP00000246194.3
RALY	ENST00000375114.7	c.829-563A>G		intron_variant	Intron 7 of 8	1		ENSP00000364255.3
RALY	ENST00000489384.1	n.34-563A>G		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.956 AC: 145482 AN: 152230 Hom.: 69604 Cov.: 34

Gnomad AFR AF: 0.985

Gnomad AMI AF: 0.996

Gnomad AMR AF: 0.975

Gnomad ASJ AF: 0.976

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.990

Gnomad FIN AF: 0.980

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.921

Gnomad OTH AF: 0.977

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.956 AC: 145599 AN: 152348 Hom.: 69662 Cov.: 34 AF XY: 0.961 AC XY: 71565 AN XY: 74492

African (AFR) AF: 0.985 AC: 40972 AN: 41576

American (AMR) AF: 0.975 AC: 14921 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.976 AC: 3388 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5184 AN: 5184

South Asian (SAS) AF: 0.990 AC: 4778 AN: 4826

European-Finnish (FIN) AF: 0.980 AC: 10422 AN: 10630

Middle Eastern (MID) AF: 0.983 AC: 289 AN: 294

European-Non Finnish (NFE) AF: 0.921 AC: 62670 AN: 68032

Other (OTH) AF: 0.977 AC: 2067 AN: 2116

Alfa AF: 0.937 Hom.: 116502

Bravo AF: 0.956

Asia WGS AF: 0.993 AC: 3455 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.6
DANN	Benign	0.54
PhyloP100		0.47
Mutation Taster		=100/0	polymorphism (auto)

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: rs6059655; hg19: chr20-32665748;