14-20781843-G-T

Variant names:

• chr14-20781843-G-T
• NM_005615.5:c.144G>T

Variant summary

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

The NM_005615.5(RNASE6):​c.144G>T​(p.Arg48Ser) 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. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RNASE6 NM_005615.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.277
• Publications: 0 publications found

Genes affected

RNASE6 (HGNC:10048): (ribonuclease A family member k6) The protein encoded by this gene is a member of the ribonuclease A superfamily and functions in the urinary tract. The protein has broad-spectrum antimicrobial activity against pathogenic bacteria. [provided by RefSeq, Nov 2014]

ENSG00000303727 (HGNC:):

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=0.07799524).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNASE6	NM_005615.5	c.144G>T	p.Arg48Ser	missense_variant	Exon 2 of 2	ENST00000304677.3	NP_005606.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNASE6	ENST00000304677.3	c.144G>T	p.Arg48Ser	missense_variant	Exon 2 of 2	1	NM_005615.5	ENSP00000302046.2
ENSG00000303727	ENST00000796740.1	n.78+18061C>A		intron_variant	Intron 1 of 2
ENSG00000303727	ENST00000796741.1	n.71+18061C>A		intron_variant	Intron 1 of 2
ENSG00000303727	ENST00000796742.1	n.64+18061C>A		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 12, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.144G>T (p.R48S) alteration is located in exon 2 (coding exon 1) of the RNASE6 gene. This alteration results from a G to T substitution at nucleotide position 144, causing the arginine (R) at amino acid position 48 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	Benign	0.14
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	12
DANN	Benign	0.84
DEOGEN2	Benign	0.0037	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.036	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.078	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.56	N
PhyloP100		0.28
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.24	N
REVEL	Benign	0.068
Sift	Benign	0.97	T
Sift4G	Benign	0.77	T
Polyphen		0.51	P
Vest4		0.13
MutPred		0.46		Gain of disorder (P = 0.0576);
MVP		0.64
MPC		0.10
ClinPred		0.10	T
GERP RS		-0.54
Varity_R		0.43
gMVP		0.39
Mutation Taster		=89/11	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

hg19: chr14-21250002;