chr16-1678333-C-G

Position:

• chr16-1678333-C-G

Variant summary

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

The NM_144570.3(JPT2):​c.21C>G​(p.Ser7Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000102 in 1,082,370 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S7G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: JPT2 NM_144570.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.341

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JPT2	NM_144570.3	c.21C>G	p.Ser7Arg	missense_variant	1/5	ENST00000248098.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JPT2	ENST00000248098.8	c.21C>G	p.Ser7Arg	missense_variant	1/5	1	NM_144570.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000102 AC: 11 AN: 1082370 Hom.: 0 Cov.: 32 AF XY: 0.00000977 AC XY: 5 AN XY: 511604

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: 0.0000120

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000151

ExAC AF: 0.0000140 AC: 1

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

Aug 02, 2021

The c.21C>G (p.S7R) alteration is located in exon 1 (coding exon 1) of the HN1L gene. This alteration results from a C to G substitution at nucleotide position 21, causing the serine (S) at amino acid position 7 to be replaced by an arginine (R). 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	0.20
BayesDel_addAF	Benign	-0.076	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.033	T;.;T;.;T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.52	T;T;T;T;T
M_CAP	Pathogenic	0.32	D
MetaRNN	Benign	0.14	T;T;T;T;T
MetaSVM	Benign	-0.55	T
MutationTaster	Benign	0.64	D;N;N;N;N
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-2.0	N;N;N;N;N
REVEL	Benign	0.051
Sift	Uncertain	0.011	D;D;D;D;D
Sift4G	Uncertain	0.048	D;D;D;D;D
Polyphen		0.77	P;.;.;.;D
Vest4		0.15
MutPred		0.16		Gain of MoRF binding (P = 0.0065);Gain of MoRF binding (P = 0.0065);Gain of MoRF binding (P = 0.0065);Gain of MoRF binding (P = 0.0065);Gain of MoRF binding (P = 0.0065);
MVP		0.093
MPC		1.3
ClinPred		0.94	D
GERP RS		3.4
Varity_R		0.21
gMVP		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.22		Position offset: -12

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

Publications

LitVar

Other links and lift over

dbSNP: rs759653499; hg19: chr16-1728334;