14-24430767-C-A

Variant names:

• chr14-24430767-C-A
• rs778163494
• NM_015299.3:c.37C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015299.3(KHNYN):​c.37C>A​(p.Arg13Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000139 in 1,438,164 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R13G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: KHNYN NM_015299.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.33
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34963295).

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.37C>A	p.Arg13Ser	missense	Exon 2 of 8	NP_056114.1	O15037
	KHNYN	NM_001290256.2		c.160C>A	p.Arg54Ser	missense	Exon 2 of 8	NP_001277185.1
	KHNYN	NM_001290257.2		c.37C>A	p.Arg13Ser	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.37C>A	p.Arg13Ser	missense	Exon 2 of 8	ENSP00000450799.1	O15037
	KHNYN	ENST00000251343.9	TSL:1	c.37C>A	p.Arg13Ser	missense	Exon 2 of 8	ENSP00000251343.5	O15037
	KHNYN	ENST00000556842.5	TSL:2	c.37C>A	p.Arg13Ser	missense	Exon 2 of 8	ENSP00000451106.1	O15037

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1438164 Hom.: 0 Cov.: 31 AF XY: 0.00000280 AC XY: 2 AN XY: 713366

African (AFR) AF: 0.0000304 AC: 1 AN: 32912

American (AMR) AF: 0.00 AC: 0 AN: 40924

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25658

East Asian (EAS) AF: 0.0000261 AC: 1 AN: 38276

South Asian (SAS) AF: 0.00 AC: 0 AN: 82896

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51702

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1100506

Other (OTH) AF: 0.00 AC: 0 AN: 59546

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-1.1	T
PhyloP100		4.3
PROVEAN	Benign	0.17	N
REVEL	Uncertain	0.30
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.22	T
Vest4		0.47
MutPred		0.50		Gain of catalytic residue at G42 (P = 0.0014)
MVP		0.67
ClinPred		0.96	D
GERP RS		4.1
PromoterAI		-0.027	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.26
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

dbSNP: rs778163494; hg19: chr14-24899973;