rs376063080

Variant names:

• chr14-21043068-G-A
• rs376063080
• NM_032572.4:c.76G>A

Your query was ambiguous. Multiple possible variants found:

• chr14-21043068-G-A
• chr14-21043068-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032572.4(RNASE7):​c.76G>A​(p.Val26Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 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. V26L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RNASE7 NM_032572.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.75

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]

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2657629).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNASE7	NM_032572.4	c.76G>A	p.Val26Ile	missense_variant	Exon 2 of 2	ENST00000298690.5	NP_115961.3
NDRG2	NM_001282211.2	c.25-19747C>T		intron_variant	Intron 1 of 14		NP_001269140.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNASE7	ENST00000298690.5	c.76G>A	p.Val26Ile	missense_variant	Exon 2 of 2	1	NM_032572.4	ENSP00000298690.3
NDRG2	ENST00000403829.7	c.25-19747C>T		intron_variant	Intron 1 of 14	2		ENSP00000385889.3
NDRG2	ENST00000555026.5	c.-7+3798C>T		intron_variant	Intron 2 of 12	5		ENSP00000451274.1
RNASE7	ENST00000481538.1	n.76G>A		non_coding_transcript_exon_variant	Exon 2 of 3	2		ENSP00000431382.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.043	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.012	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.77	D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.37	T
MutationAssessor	Uncertain	2.2	M
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.040	N
REVEL	Benign	0.26
Sift	Uncertain	0.028	D
Sift4G	Benign	0.27	T
Polyphen		1.0	D
Vest4		0.14
MutPred		0.37		Gain of catalytic residue at K29 (P = 0.0042);
MVP		0.86
MPC		0.23
ClinPred		0.59	D
GERP RS		5.1
Varity_R		0.071
gMVP		0.35

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: rs376063080; hg19: chr14-21511227;