16-1678322-G-C

Position:

• chr16-1678322-G-C

Variant summary

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

The NM_144570.3(JPT2):​c.10G>C​(p.Val4Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/19 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: JPT2 NM_144570.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.15

Genes affected

JPT2 (HGNC:14137): (Jupiter microtubule associated homolog 2) Located in cytosol and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.12587398).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JPT2	NM_144570.3	c.10G>C	p.Val4Leu	missense_variant	1/5	ENST00000248098.8	NP_653171.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JPT2	ENST00000248098.8	c.10G>C	p.Val4Leu	missense_variant	1/5	1	NM_144570.3	ENSP00000248098	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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

Apr 07, 2022

The c.10G>C (p.V4L) alteration is located in exon 1 (coding exon 1) of the HN1L gene. This alteration results from a G to C substitution at nucleotide position 10, causing the valine (V) at amino acid position 4 to be replaced by a leucine (L). 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	0.18
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	22
DANN	Benign	0.68
DEOGEN2	Benign	0.027	T;.;T;.;T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.56
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.41	T;T;T;T;T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.13	T;T;T;T;T
MetaSVM	Benign	-0.88	T
MutationTaster	Benign	1.0	D;N;N;N;N
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.77	N;N;N;N;N
REVEL	Benign	0.13
Sift	Uncertain	0.0070	D;T;D;T;T
Sift4G	Uncertain	0.025	D;T;D;T;T
Polyphen		0.0010	B;.;.;.;B
Vest4		0.084
MutPred		0.11		Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);
MVP		0.12
MPC		0.49
ClinPred		0.53	D
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.12
gMVP		0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr16-1728323;