16-22534092-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001395849.1(NPIPB5):c.1109C>T(p.Ala370Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 10)
  • Exomes 𝑓: 0.0000066 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NPIPB5 NM_001395849.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.00100

Genes affected

NPIPB5 (HGNC:37233): (nuclear pore complex interacting protein family member B5) Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

LOC105371131 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.12727979).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPIPB5	NM_001395849.1	c.1109C>T	p.Ala370Val	missense_variant	7/7	ENST00000424340.7
LOC105371131	XR_007065022.1	n.150+3386G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPIPB5	ENST00000424340.7	c.1109C>T	p.Ala370Val	missense_variant	7/7	1	NM_001395849.1	P1

Frequencies

GnomAD3 genomes Cov.: 10

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000658 AC: 7 AN: 1064044 Hom.: 0 Cov.: 16 AF XY: 0.00000921 AC XY: 5 AN XY: 543048

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000102

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: 0.00000261

Gnomad4 OTH exome AF: 0.0000207

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

Feb 23, 2023

The c.1109C>T (p.A370V) alteration is located in exon 7 (coding exon 7) of the NPIPB5 gene. This alteration results from a C to T substitution at nucleotide position 1109, causing the alanine (A) at amino acid position 370 to be replaced by a valine (V). 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	Uncertain	0.36
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.60
Cadd	Benign	13
Dann	Uncertain	0.99
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.0077	N
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.13	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N
PROVEAN	Benign	-0.79	N;.;N;N;N;.
REVEL	Benign	0.090
Sift	Benign	0.11	T;.;D;D;T;.
Sift4G	Benign	0.30	T;T;T;T;T;T
Polyphen		0.99	.;.;D;D;.;.
Vest4		0.10, 0.11, 0.14, 0.081
MutPred		0.17		Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);.;
MVP		0.030
ClinPred		0.23	T
Varity_R		0.055
gMVP		0.0048

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: rs1489448058; hg19: chr16-22545413;