rs776661234

Variant names:

• chr20-34077075-G-A
• rs776661234
• NM_016732.3:c.706G>A

Your query was ambiguous. Multiple possible variants found:

• chr20-34077075-G-A
• chr20-34077075-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016732.3(RALY):​c.706G>A​(p.Gly236Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000344 in 1,453,800 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. G236R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: RALY NM_016732.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0440
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07379043).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016732.3. 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
	RALY	NM_016732.3	MANE Select	c.706G>A	p.Gly236Ser	missense	Exon 8 of 10	NP_057951.1	Q9UKM9-1
	RALY	NM_007367.4		c.658G>A	p.Gly220Ser	missense	Exon 7 of 9	NP_031393.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RALY	ENST00000246194.8	TSL:1 MANE Select	c.706G>A	p.Gly236Ser	missense	Exon 8 of 10	ENSP00000246194.3	Q9UKM9-1
	RALY	ENST00000375114.7	TSL:1	c.658G>A	p.Gly220Ser	missense	Exon 7 of 9	ENSP00000364255.3	Q9UKM9-2
	RALY	ENST00000874581.1		c.706G>A	p.Gly236Ser	missense	Exon 8 of 10	ENSP00000544640.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 225568 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.00

GnomAD4 exome AF: 0.00000344 AC: 5 AN: 1453800 Hom.: 0 Cov.: 34 AF XY: 0.00000277 AC XY: 2 AN XY: 722756

African (AFR) AF: 0.00 AC: 0 AN: 33326

American (AMR) AF: 0.00 AC: 0 AN: 43926

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25908

East Asian (EAS) AF: 0.00 AC: 0 AN: 39526

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85552

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51664

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5718

European-Non Finnish (NFE) AF: 0.00000271 AC: 3 AN: 1108244

Other (OTH) AF: 0.0000167 AC: 1 AN: 59936

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	0.00021	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	0.19
DANN	Benign	0.63
DEOGEN2	Benign	0.037	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.061	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-0.66	T
MutationAssessor	Benign	-0.76	N
PhyloP100		-0.044
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	0.52	N
REVEL	Uncertain	0.30
Sift	Benign	0.73	T
Sift4G	Benign	0.19	T
Polyphen		0.0010	B
Vest4		0.20
MutPred		0.32		Gain of phosphorylation at G236 (P = 6e-04)
MVP		0.79
MPC		0.53
ClinPred		0.052	T
GERP RS		-1.2
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.7
Varity_R		0.040
gMVP		0.31
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs776661234; hg19: chr20-32664881;