16-1685495-C-A

Variant names:

• chr16-1685495-C-A
• rs1230379534
• NM_144570.3:c.101C>A

Variant summary

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

The NM_144570.3(JPT2):​c.101C>A​(p.Ala34Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: JPT2 NM_144570.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.831

Genes affected

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

ENSG00000261732 (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=0.07068154).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JPT2	NM_144570.3	c.101C>A	p.Ala34Asp	missense_variant	Exon 2 of 5	ENST00000248098.8	NP_653171.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JPT2	ENST00000248098.8	c.101C>A	p.Ala34Asp	missense_variant	Exon 2 of 5	1	NM_144570.3	ENSP00000248098.3
ENSG00000261732	ENST00000454337.1	n.*3908C>A		non_coding_transcript_exon_variant	Exon 22 of 23	2		ENSP00000399780.1
ENSG00000261732	ENST00000454337.1	n.*3908C>A		3_prime_UTR_variant	Exon 22 of 23	2		ENSP00000399780.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251476 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135912

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461858 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727230

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 09, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.101C>A (p.A34D) alteration is located in exon 2 (coding exon 2) of the HN1L gene. This alteration results from a C to A substitution at nucleotide position 101, causing the alanine (A) at amino acid position 34 to be replaced by an aspartic acid (D). 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	0.12
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.010	T;.;T;.;.;T;T;.;T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.74	T;T;T;T;T;T;T;T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.071	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.91	T
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.47	N;N;N;N;N;N;N;N;N
REVEL	Benign	0.11
Sift	Benign	0.28	T;T;T;T;T;T;T;T;T
Sift4G	Benign	0.31	T;T;T;T;T;D;T;T;T
Polyphen		0.96	D;.;.;.;.;B;.;P;.
Vest4		0.30
MutPred		0.14		.;Loss of glycosylation at T63 (P = 0.0943);.;.;.;Loss of glycosylation at T63 (P = 0.0943);.;.;.;
MVP		0.15
MPC		1.3
ClinPred		0.36	T
GERP RS		-2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.058
gMVP		0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1230379534; hg19: chr16-1735496;