rs1243469

Variant names:

• chr14-21043338-C-G
• rs1243469
• NM_032572.4:c.346C>G

Your query was ambiguous. Multiple possible variants found:

• chr14-21043338-C-G
• chr14-21043338-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032572.4(RNASE7):​c.346C>G​(p.His116Asp) 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. 14/21 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. H116Y) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RNASE7 NM_032572.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.168

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11167273).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNASE7	NM_032572.4	c.346C>G	p.His116Asp	missense_variant	Exon 2 of 2	ENST00000298690.5	NP_115961.3
NDRG2	NM_001282211.2	c.25-20017G>C		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.346C>G	p.His116Asp	missense_variant	Exon 2 of 2	1	NM_032572.4	ENSP00000298690.3
NDRG2	ENST00000403829.7	c.25-20017G>C		intron_variant	Intron 1 of 14	2		ENSP00000385889.3
NDRG2	ENST00000555026.5	c.-7+3528G>C		intron_variant	Intron 2 of 12	5		ENSP00000451274.1
RNASE7	ENST00000481538.1	n.346C>G		non_coding_transcript_exon_variant	Exon 2 of 3	2		ENSP00000431382.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 59

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.087	T
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.042	N
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.26	N
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.15
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0090	D
Polyphen		0.0010	B
Vest4		0.22
MutPred		0.51		Gain of catalytic residue at S113 (P = 0.0177);
MVP		0.59
MPC		0.28
ClinPred		0.22	T
GERP RS		2.7
Varity_R		0.37
gMVP		0.66

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: rs1243469; hg19: chr14-21511497;