Genetic Variant RNASE7:p.His116Tyr (chr14-21043338-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_032572.4(RNASE7):c.346C>T(p.His116Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.874 in 1,614,008 control chromosomes in the GnomAD database, including 618,677 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.86 ( 56409 hom., cov: 32)

Exomes 𝑓: 0.88 ( 562268 hom. )

Consequence

RNASE7
NM_032572.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.168

Variant links:

Genes affected

RNASE7 (HGNC:19278): (ribonuclease A family member 7) The protein encoded by this gene belongs to the pancreatic ribonuclease family, a subset of the ribonuclease A superfamily. The protein has broad-spectrum antimicrobial activity against bacteria and fungi. [provided by RefSeq, Oct 2014]

RNASE7 links:

NDRG2 (HGNC:14460): (NDRG family member 2) This gene is a member of the N-myc downregulated gene family which belongs to the alpha/beta hydrolase superfamily. The protein encoded by this gene is a cytoplasmic protein that may play a role in neurite outgrowth. This gene may be involved in glioblastoma carcinogenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2017]

NDRG2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.2297834E-7).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.89 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNASE7	NM_032572.4 link	c.346C>T	p.His116Tyr	missense_variant	Exon 2 of 2	ENST00000298690.5	NP_115961.3	Q9H1E1
NDRG2	NM_001282211.2 link	c.25-20017G>A		intron_variant	Intron 1 of 14		NP_001269140.1	Q9UN36-6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RNASE7	ENST00000298690.5 link	c.346C>T	p.His116Tyr	missense_variant	Exon 2 of 2	1	NM_032572.4	ENSP00000298690.3	Q9H1E1
NDRG2	ENST00000403829.7 link	c.25-20017G>A		intron_variant	Intron 1 of 14	2		ENSP00000385889.3	Q9UN36-6
NDRG2	ENST00000555026.5 link	c.-7+3528G>A		intron_variant	Intron 2 of 12	5		ENSP00000451274.1	G3V5H8
RNASE7	ENST00000481538.1 link	n.346C>T		non_coding_transcript_exon_variant	Exon 2 of 3	2		ENSP00000431382.1	Q9H1E1

Frequencies

GnomAD3 genomes

AF:

0.859

AC:

130657

AN:

152068

Hom.:

56362

Cov.:

show subpopulations

Gnomad AFR

AF:

0.786

Gnomad AMI

AF:

0.886

Gnomad AMR

AF:

0.902

Gnomad ASJ

AF:

0.938

Gnomad EAS

AF:

0.873

Gnomad SAS

AF:

0.743

Gnomad FIN

AF:

0.938

Gnomad MID

AF:

0.832

Gnomad NFE

AF:

0.885

Gnomad OTH

AF:

0.867

GnomAD3 exomes

AF:

0.873

AC:

219245

AN:

251142

Hom.:

96292

AF XY:

0.866

AC XY:

117638

AN XY:

135814

show subpopulations

Gnomad AFR exome

AF:

0.785

Gnomad AMR exome

AF:

0.929

Gnomad ASJ exome

AF:

0.943

Gnomad EAS exome

AF:

0.863

Gnomad SAS exome

AF:

0.737

Gnomad FIN exome

AF:

0.937

Gnomad NFE exome

AF:

0.888

Gnomad OTH exome

AF:

0.879

GnomAD4 exome

AF:

0.876

AC:

1280316

AN:

1461822

Hom.:

562268

Cov.:

AF XY:

0.872

AC XY:

634031

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.783

Gnomad4 AMR exome

AF:

0.925

Gnomad4 ASJ exome

AF:

0.941

Gnomad4 EAS exome

AF:

0.891

Gnomad4 SAS exome

AF:

0.740

Gnomad4 FIN exome

AF:

0.937

Gnomad4 NFE exome

AF:

0.883

Gnomad4 OTH exome

AF:

0.871

GnomAD4 genome

AF:

0.859

AC:

130761

AN:

152186

Hom.:

56409

Cov.:

AF XY:

0.859

AC XY:

63943

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.786

Gnomad4 AMR

AF:

0.903

Gnomad4 ASJ

AF:

0.938

Gnomad4 EAS

AF:

0.874

Gnomad4 SAS

AF:

0.744

Gnomad4 FIN

AF:

0.938

Gnomad4 NFE

AF:

0.885

Gnomad4 OTH

AF:

0.869

Alfa

AF:

0.879

Hom.:

146229

Bravo

AF:

0.856

TwinsUK

AF:

0.885

AC:

3282

ALSPAC

AF:

0.882

AC:

3399

ESP6500AA

AF:

0.791

AC:

3486

ESP6500EA

AF:

0.885

AC:

7608

ExAC

AF:

0.866

AC:

105173

Asia WGS

AF:

0.825

AC:

2867

AN:

3478

EpiCase

AF:

0.881

EpiControl

AF:

0.890

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.042

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.46

CADD

Benign

6.3

DANN

Benign

0.89

DEOGEN2

Benign

0.0083

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.00077

MetaRNN

Benign

8.2e-7

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-3.2

PrimateAI

Benign

0.40

PROVEAN

Benign

4.5

REVEL

Benign

0.12

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.070

MPC

0.24

ClinPred

0.0032

GERP RS

2.7

Varity_R

0.034

gMVP

0.41

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over