16-1678331-A-G

Position:

• chr16-1678331-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_144570.3(JPT2):​c.19A>G​(p.Ser7Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000369 in 1,083,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S7R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000037 (0 hom.)
• Consequence: JPT2 NM_144570.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.126

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04665464).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JPT2	NM_144570.3	c.19A>G	p.Ser7Gly	missense_variant	1/5	ENST00000248098.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JPT2	ENST00000248098.8	c.19A>G	p.Ser7Gly	missense_variant	1/5	1	NM_144570.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000369 AC: 4 AN: 1083756 Hom.: 0 Cov.: 32 AF XY: 0.00000390 AC XY: 2 AN XY: 512332

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000380

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000218

Gnomad4 OTH exome AF: 0.0000230

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

Feb 28, 2024

The c.19A>G (p.S7G) alteration is located in exon 1 (coding exon 1) of the HN1L gene. This alteration results from a A to G substitution at nucleotide position 19, causing the serine (S) at amino acid position 7 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	0.054
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	8.5
DANN	Benign	0.78
DEOGEN2	Benign	0.024	T;.;T;.;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.085	N
LIST_S2	Benign	0.40	T;T;T;T;T
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.047	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.3	N;N;N;N;N
REVEL	Benign	0.022
Sift	Benign	0.20	T;T;T;T;T
Sift4G	Benign	0.13	T;T;T;T;T
Polyphen		0.0	B;.;.;.;B
Vest4		0.054
MutPred		0.20		Loss of phosphorylation at S7 (P = 0.0382);Loss of phosphorylation at S7 (P = 0.0382);Loss of phosphorylation at S7 (P = 0.0382);Loss of phosphorylation at S7 (P = 0.0382);Loss of phosphorylation at S7 (P = 0.0382);
MVP		0.15
MPC		0.45
ClinPred		0.060	T
GERP RS		0.72
Varity_R		0.062
gMVP		0.14

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-1728332;