14-21043459-T-C

Variant names:

• chr14-21043459-T-C
• NM_032572.4:c.467T>C

Variant summary

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

The NM_032572.4(RNASE7):​c.467T>C​(p.Leu156Pro) 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. 12/21 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: RNASE7 NM_032572.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.430

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=0.18609244).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNASE7	NM_032572.4	c.467T>C	p.Leu156Pro	missense_variant	Exon 2 of 2	ENST00000298690.5	NP_115961.3
NDRG2	NM_001282211.2	c.25-20138A>G		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.467T>C	p.Leu156Pro	missense_variant	Exon 2 of 2	1	NM_032572.4	ENSP00000298690.3
NDRG2	ENST00000403829.7	c.25-20138A>G		intron_variant	Intron 1 of 14	2		ENSP00000385889.3
NDRG2	ENST00000555026.5	c.-7+3407A>G		intron_variant	Intron 2 of 12	5		ENSP00000451274.1
RNASE7	ENST00000481538.1	n.467T>C		non_coding_transcript_exon_variant	Exon 2 of 3	2		ENSP00000431382.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 06, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.467T>C (p.L156P) alteration is located in exon 2 (coding exon 1) of the RNASE7 gene. This alteration results from a T to C substitution at nucleotide position 467, causing the leucine (L) at amino acid position 156 to be replaced by a proline (P). 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	Uncertain	0.43
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.069	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.038	N
M_CAP	Benign	0.082	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.75	T
MutationAssessor	Uncertain	2.0	M
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.26
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.76	P
Vest4		0.12
MutPred		0.52		Gain of catalytic residue at D153 (P = 0.0103);
MVP		0.60
MPC		0.81
ClinPred		0.94	D
GERP RS		2.8
Varity_R		0.41
gMVP		0.48

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-21511618;