chr14-24430818-C-A

Variant names:

• chr14-24430818-C-A
• NM_015299.3:c.88C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015299.3(KHNYN):​c.88C>A​(p.His30Asn) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: KHNYN NM_015299.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0710
• Publications: 0 publications found

Genes affected

KHNYN (HGNC:20166): (KH and NYN domain containing) The protein encoded by this gene contains a ribonuclease NYN domain and belongs to the N4BP1 family. The protein is a cofactor for the zinc finger antiviral protein (ZAP protein) which targets viral RNA for degradation and restricts SARS-CoV-2 infection. [provided by RefSeq, Sep 2021]

CBLN3 (HGNC:20146): (cerebellin 3 precursor) Members of the precerebellin family, such as CBLN3, contain a cerebellin motif (see CBLN1; MIM 600432) and a C-terminal C1q signature domain (see MIM 120550) that mediates trimeric assembly of atypical collagen complexes. However, precerebellins do not contain a collagen motif, suggesting that they are not conventional components of the extracellular matrix (Pang et al., 2000 [PubMed 10964938]).[supplied by OMIM, Aug 2009]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09252724).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015299.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KHNYN	NM_015299.3	MANE Select	c.88C>A	p.His30Asn	missense	Exon 2 of 8	NP_056114.1	O15037
	KHNYN	NM_001290256.2		c.211C>A	p.His71Asn	missense	Exon 2 of 8	NP_001277185.1
	KHNYN	NM_001290257.2		c.88C>A	p.His30Asn	missense	Exon 2 of 8	NP_001277186.1	O15037

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KHNYN	ENST00000553935.6	TSL:1 MANE Select	c.88C>A	p.His30Asn	missense	Exon 2 of 8	ENSP00000450799.1	O15037
	KHNYN	ENST00000251343.9	TSL:1	c.88C>A	p.His30Asn	missense	Exon 2 of 8	ENSP00000251343.5	O15037
	CBLN3	ENST00000859360.1		c.-413G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 4	ENSP00000529419.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	5.1
DANN	Benign	0.93
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.87
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.093	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.60	N
PhyloP100		-0.071
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.017
Sift	Benign	0.34	T
Sift4G	Benign	0.35	T
Polyphen		0.0	B
Vest4		0.21
MutPred		0.23		Gain of catalytic residue at F35 (P = 0.0663)
MVP		0.37
MPC		0.28
ClinPred		0.056	T
GERP RS		-3.9
PromoterAI		0.047	Neutral
Varity_R		0.059
gMVP		0.45
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

hg19: chr14-24900024;