16-19714131-T-C

Position:

• chr16-19714131-T-C

Variant summary

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

The NM_001012991.3(KNOP1):​c.905A>G​(p.Asp302Gly) 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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KNOP1 NM_001012991.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.298

Genes affected

KNOP1 (HGNC:34404): (lysine rich nucleolar protein 1) The protein encoded by this gene is a nucleolar protein that interacts with zinc finger 106 protein. The encoded protein has several of the same characteristics as nucleostemin and may be involved in testis development. [provided by RefSeq, Feb 2017]

KNOP1 (HGNC:):

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=0.07356331).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KNOP1	NM_001012991.3	c.905A>G	p.Asp302Gly	missense_variant	2/5	ENST00000219837.12	NP_001013009.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KNOP1	ENST00000219837.12	c.905A>G	p.Asp302Gly	missense_variant	2/5	1	NM_001012991.3	ENSP00000219837.7
KNOP1	ENST00000567367.1	c.446A>G	p.Asp149Gly	missense_variant	1/3	3		ENSP00000455369.1
KNOP1	ENST00000565844.1	n.985A>G		non_coding_transcript_exon_variant	2/4	5
ENSG00000261312	ENST00000565916.1	n.782-655T>C		intron_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 26, 2024

The c.905A>G (p.D302G) alteration is located in exon 2 (coding exon 1) of the KNOP1 gene. This alteration results from a A to G substitution at nucleotide position 905, causing the aspartic acid (D) at amino acid position 302 to be replaced by a glycine (G). 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	Benign	0.14
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	13
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.036
Sift	Uncertain	0.015	D
Sift4G	Benign	0.16	T
Polyphen		0.0040	B
Vest4		0.12
MutPred		0.16		Gain of MoRF binding (P = 0.0814);
MVP		0.19
MPC		0.12
ClinPred		0.085	T
GERP RS		0.76
Varity_R		0.15
gMVP		0.027

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr16-19725453;