17-75147561-G-T

Position:

• chr17-75147561-G-T

Variant summary

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

The NM_016185.4(JPT1):​c.292C>A​(p.Leu98Met) 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. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: JPT1 NM_016185.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.55

Genes affected

JPT1 (HGNC:14569): (Jupiter microtubule associated homolog 1) Located in nuclear membrane; nucleolus; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

LOC107985034 (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=0.2126809).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JPT1	NM_016185.4	c.292C>A	p.Leu98Met	missense_variant	3/5	ENST00000409753.8
LOC107985034	XR_007065907.1	n.4628-876G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JPT1	ENST00000409753.8	c.292C>A	p.Leu98Met	missense_variant	3/5	1	NM_016185.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1459392 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 726156

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

May 11, 2022

The c.292C>A (p.L98M) alteration is located in exon 3 (coding exon 3) of the HN1 gene. This alteration results from a C to A substitution at nucleotide position 292, causing the leucine (L) at amino acid position 98 to be replaced by a methionine (M). 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	0.082
BayesDel_addAF	Benign	-0.079	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.020	.;T;.;.;.;.;T;T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.76	.;T;.;T;.;T;T;T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.21	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.85	T
MutationTaster	Benign	0.76	N;N;N;N;N;N;N;N;N;N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.12	.;N;.;N;.;.;.;.
REVEL	Benign	0.044
Sift	Benign	0.16	.;T;.;T;.;.;.;.
Sift4G	Benign	0.14	T;T;T;T;T;T;.;T
Polyphen		0.98, 0.98	.;D;.;D;.;.;.;.
Vest4		0.34
MutPred		0.31		.;Loss of sheet (P = 0.1907);.;Loss of sheet (P = 0.1907);.;.;.;Loss of sheet (P = 0.1907);
MVP		0.51
MPC		0.84
ClinPred		0.75	D
GERP RS		4.7
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.1
Varity_R		0.20
gMVP		0.017

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-73143656;