14-20699417-A-G

Position:

• chr14-20699417-A-G

Variant summary

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

The NM_002937.5(RNASE4):​c.46A>G​(p.Thr16Ala) variant causes a missense 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. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T16S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RNASE4 NM_002937.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01

Genes affected

RNASE4 (HGNC:10047): (ribonuclease A family member 4) The protein encoded by this gene belongs to the pancreatic ribonuclease family. It plays an important role in mRNA cleavage and has marked specificity towards the 3' side of uridine nucleotides. Alternative splicing results in four transcript variants encoding the same protein. This gene and the gene that encodes angiogenin share promoters and 5' exons. Each gene splices to a unique downstream exon that contains its complete coding region. [provided by RefSeq, Aug 2013]

ENSG00000259171 (HGNC:):

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=0.15860566).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNASE4	NM_002937.5	c.46A>G	p.Thr16Ala	missense_variant	2/2	ENST00000555835.3	NP_002928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNASE4	ENST00000555835.3	c.46A>G	p.Thr16Ala	missense_variant	2/2	1	NM_002937.5	ENSP00000452245.1
ENSG00000259171	ENST00000553909.1	c.*53A>G		3_prime_UTR_variant	3/3	2		ENSP00000477037.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.029	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0024	T;T;T
Eigen	Benign	-0.15
Eigen_PC	Benign	0.021
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.53	.;.;T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.16	T;T;T
MetaSVM	Benign	-0.55	T
MutationAssessor	Benign	1.2	L;L;L
PrimateAI	Benign	0.42	T
PROVEAN	Benign	0.21	N;N;N
REVEL	Benign	0.27
Sift	Benign	0.12	T;T;T
Sift4G	Benign	0.71	T;T;T
Polyphen		0.29	B;B;B
Vest4		0.17
MutPred		0.39		Gain of catalytic residue at L20 (P = 0.0571);Gain of catalytic residue at L20 (P = 0.0571);Gain of catalytic residue at L20 (P = 0.0571);
MVP		0.69
MPC		0.12
ClinPred		0.25	T
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.048
gMVP		0.42

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: rs3748338; hg19: chr14-21167576;