rs3748338

Variant names:

• chr14-20699417-A-C
• rs3748338
• NM_002937.5:c.46A>C

Your query was ambiguous. Multiple possible variants found:

• chr14-20699417-A-C
• chr14-20699417-A-G
• chr14-20699417-A-T

Variant summary

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

The NM_002937.5(RNASE4):​c.46A>C​(p.Thr16Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000618 in 1,456,724 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: RNASE4 NM_002937.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01
• Publications: 25 publications found

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:):

EGILA (HGNC:54482): (EGFR interacting lncRNA)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNASE4	NM_002937.5	c.46A>C	p.Thr16Pro	missense_variant	Exon 2 of 2	ENST00000555835.3	NP_002928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNASE4	ENST00000555835.3	c.46A>C	p.Thr16Pro	missense_variant	Exon 2 of 2	1	NM_002937.5	ENSP00000452245.1
ENSG00000259171	ENST00000553909.1	c.*53A>C		3_prime_UTR_variant	Exon 3 of 3	2		ENSP00000477037.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000618 AC: 9 AN: 1456724 Hom.: 0 Cov.: 32 AF XY: 0.00000415 AC XY: 3 AN XY: 723712

African (AFR) AF: 0.00 AC: 0 AN: 33402

American (AMR) AF: 0.00 AC: 0 AN: 44616

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26030

East Asian (EAS) AF: 0.00 AC: 0 AN: 39542

South Asian (SAS) AF: 0.00 AC: 0 AN: 86144

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52746

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.00000812 AC: 9 AN: 1108364

Other (OTH) AF: 0.00 AC: 0 AN: 60134

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 946

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0067	T;T;T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.61	.;.;T
M_CAP	Benign	0.067	D
MetaRNN	Uncertain	0.55	D;D;D
MetaSVM	Uncertain	0.20	D
MutationAssessor	Uncertain	2.6	M;M;M
PhyloP100		1.0
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.5	N;N;N
REVEL	Uncertain	0.57
Sift	Uncertain	0.0050	D;D;D
Sift4G	Benign	0.33	T;T;T
Polyphen		1.0	D;D;D
Vest4		0.46
MutPred		0.63		Gain of catalytic residue at L15 (P = 0.0011);Gain of catalytic residue at L15 (P = 0.0011);Gain of catalytic residue at L15 (P = 0.0011);
MVP		0.80
MPC		0.52
ClinPred		0.84	D
GERP RS		4.1
Varity_R		0.38
gMVP		0.54
Mutation Taster		=91/9	polymorphism

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: rs3748338; hg19: chr14-21167576;