chr14-20781791-C-A

Variant names:

• chr14-20781791-C-A
• rs200834282
• NM_005615.5:c.92C>A

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_005615.5(RNASE6):​c.92C>A​(p.Ala31Asp) 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 pathogenic 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. A31G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RNASE6 NM_005615.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03
• 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.945

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNASE6	NM_005615.5	c.92C>A	p.Ala31Asp	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.92C>A	p.Ala31Asp	missense_variant	Exon 2 of 2	1	NM_005615.5	ENSP00000302046.2
ENSG00000303727	ENST00000796740.1	n.78+18113G>T		intron_variant	Intron 1 of 2
ENSG00000303727	ENST00000796741.1	n.71+18113G>T		intron_variant	Intron 1 of 2
ENSG00000303727	ENST00000796742.1	n.64+18113G>T		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251466 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: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.19
Eigen_PC	Benign	-0.036
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.082	D
MetaRNN	Pathogenic	0.95	D
MetaSVM	Uncertain	-0.24	T
MutationAssessor	Pathogenic	3.6	H
PhyloP100		1.0
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-4.2	D
REVEL	Uncertain	0.50
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.58
MutPred		0.78		Gain of methylation at K26 (P = 0.0433);
MVP		0.97
MPC		0.55
ClinPred		0.92	D
GERP RS		4.2
Varity_R		0.87
gMVP		0.89
Mutation Taster		=80/20	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: rs200834282; hg19: chr14-21249950;