17-75147590-G-A

Position:

• chr17-75147590-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1 PM2 BP4_Moderate

The NM_016185.4(JPT1):​c.263C>T​(p.Ser88Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,716 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: JPT1 NM_016185.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.46

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 2 ACMG points.

• PM1: In a modified_residue Phosphoserine (size 0) in uniprot entity JUPI1_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2324264).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JPT1	NM_016185.4	c.263C>T	p.Ser88Phe	missense_variant	3/5	ENST00000409753.8	NP_057269.1
LOC107985034	XR_007065907.1	n.4628-847G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JPT1	ENST00000409753.8	c.263C>T	p.Ser88Phe	missense_variant	3/5	1	NM_016185.4	ENSP00000387059	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461716 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727166

Gnomad4 AFR exome AF: 0.0000299

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

Jun 17, 2024

The c.263C>T (p.S88F) alteration is located in exon 3 (coding exon 3) of the HN1 gene. This alteration results from a C to T substitution at nucleotide position 263, causing the serine (S) at amino acid position 88 to be replaced by a phenylalanine (F). 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	0.17
BayesDel_addAF	Benign	-0.0070	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.041	.;T;.;.;.;.;T;T
Eigen	Benign	0.033
Eigen_PC	Benign	0.035
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.89	.;D;.;D;.;D;D;D
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.23	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationTaster	Benign	1.0	N;N;N;N;N;N;N;N;N;N
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	-2.2	.;N;.;N;.;.;.;.
REVEL	Benign	0.088
Sift	Uncertain	0.011	.;D;.;D;.;.;.;.
Sift4G	Uncertain	0.039	D;D;D;D;D;D;.;D
Polyphen		0.96, 0.57	.;D;.;P;.;.;.;.
Vest4		0.33
MutPred		0.28		.;Loss of phosphorylation at S88 (P = 0.006);.;Loss of phosphorylation at S88 (P = 0.006);.;.;.;Loss of phosphorylation at S88 (P = 0.006);
MVP		0.50
MPC		0.91
ClinPred		0.88	D
GERP RS		4.3
Varity_R		0.15
gMVP		0.027

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: chr17-73143685;