8-84774634-G-C

Position:

• chr8-84774634-G-C

Variant summary

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

The NM_173848.7(RALYL):​c.312G>C​(p.Arg104Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RALYL NM_173848.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.59

Genes affected

RALYL (HGNC:27036): (RALY RNA binding protein like) Enables identical protein binding activity. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RALYL	NM_173848.7	c.312G>C	p.Arg104Ser	missense_variant	3/9	ENST00000521268.6	NP_776247.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RALYL	ENST00000521268.6	c.312G>C	p.Arg104Ser	missense_variant	3/9	1	NM_173848.7	ENSP00000430367.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 10, 2023

The c.351G>C (p.R117S) alteration is located in exon 3 (coding exon 3) of the RALYL gene. This alteration results from a G to C substitution at nucleotide position 351, causing the arginine (R) at amino acid position 117 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Uncertain	0.091	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T;T;T;.;.;.;.
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Pathogenic	0.97	.;.;D;D;D;D;D
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.72	D;D;D;D;D;D;D
MetaSVM	Benign	-0.43	T
MutationAssessor	Benign	2.0	M;M;M;.;.;.;.
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-3.8	D;D;D;D;D;D;D
REVEL	Benign	0.28
Sift	Uncertain	0.0010	D;D;D;D;D;D;D
Sift4G	Uncertain	0.0040	D;D;D;T;D;D;D
Polyphen		0.99	D;D;D;P;.;P;.
Vest4		0.69
MutPred		0.55		Gain of glycosylation at R104 (P = 0.0114);Gain of glycosylation at R104 (P = 0.0114);Gain of glycosylation at R104 (P = 0.0114);Gain of glycosylation at R104 (P = 0.0114);.;.;.;
MVP		0.62
MPC		0.13
ClinPred		0.99	D
GERP RS		4.0
Varity_R		0.70
gMVP		0.69

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-85686869;