16-14945871-A-C

Position:

• chr16-14945871-A-C

Variant summary

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

The NM_006985.4(NPIPA1):​c.327A>C​(p.Leu109Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 10)
• Consequence: NPIPA1 NM_006985.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.120

Genes affected

NPIPA1 (HGNC:7909): (nuclear pore complex interacting protein family member A1) Predicted to be involved in mRNA transport and protein transport. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

PKD1P3-NPIPA1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPIPA1	NM_006985.4	c.327A>C	p.Leu109Phe	missense_variant	4/8	ENST00000328085.10
PKD1P3-NPIPA1	NR_146231.1	n.6534A>C		non_coding_transcript_exon_variant	34/39

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPIPA1	ENST00000328085.10	c.327A>C	p.Leu109Phe	missense_variant	4/8	1	NM_006985.4	P1

Frequencies

GnomAD3 genomes Cov.: 10

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 10

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 12, 2021

The c.327A>C (p.L109F) alteration is located in exon 4 (coding exon 4) of the NPIPA1 gene. This alteration results from a A to C substitution at nucleotide position 327, causing the leucine (L) at amino acid position 109 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	0.34
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.041	T;.
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.0016	N
LIST_S2	Benign	0.85	T;T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.34	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.1	M;.
MutationTaster	Benign	1.0	N
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.17
Sift	Benign	0.092	T;D
Sift4G	Benign	0.13	T;T
Polyphen		0.99	D;.
Vest4		0.070
MutPred		0.70		Gain of sheet (P = 0.0477);.;
MVP		0.055
MPC		3.1
ClinPred		0.54	D
GERP RS		0.11
Varity_R		0.14
gMVP		0.0011

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.21		Position offset: 10

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: chr16-15039728;