Variant chr16-568277-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001301159.2(NHLRC4):c.230G>C(p.Arg77Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

NHLRC4
NM_001301159.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.499

Variant links:

Genes affected

NHLRC4 (HGNC:26700): (NHL repeat containing 4) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in protein K48-linked ubiquitination. [provided by Alliance of Genome Resources, Apr 2022]

NHLRC4 links:

PIGQ (HGNC:14135): (phosphatidylinositol glycan anchor biosynthesis class Q) This gene is involved in the first step in glycosylphosphatidylinositol (GPI)-anchor biosynthesis. The GPI-anchor is a glycolipid found on many blood cells and serves to anchor proteins to the cell surface. This gene encodes a N-acetylglucosaminyl transferase component that is part of the complex that catalyzes transfer of N-acetylglucosamine (GlcNAc) from UDP-GlcNAc to phosphatidylinositol (PI). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2012]

PIGQ links:

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ACMG classification

Classification made for transcript

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=0.09415454).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NHLRC4	NM_001301159.2 linkuse as main transcript	c.230G>C	p.Arg77Pro	missense_variant	2/2	ENST00000424439.3	NP_001288088.1	P0CG21
NHLRC4	NM_176677.3 linkuse as main transcript	c.230G>C	p.Arg77Pro	missense_variant	2/2		NP_788850.1	P0CG21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NHLRC4	ENST00000424439.3 linkuse as main transcript	c.230G>C	p.Arg77Pro	missense_variant	2/2	3	NM_001301159.2	ENSP00000410858.2	P0CG21
NHLRC4	ENST00000540585.1 linkuse as main transcript	c.230G>C	p.Arg77Pro	missense_variant	2/2	1		ENSP00000442223.1	P0CG21
PIGQ	ENST00000409527.6 linkuse as main transcript	c.-10+714G>C		intron_variant		2		ENSP00000386760.2	Q9BRB3-2
PIGQ	ENST00000293874.2 linkuse as main transcript	c.-10+714G>C		intron_variant		4		ENSP00000293874.2	J3QTH6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459870

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726208

show subpopulations

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 12, 2024

The c.230G>C (p.R77P) alteration is located in exon 2 (coding exon 1) of the NHLRC4 gene. This alteration results from a G to C substitution at nucleotide position 230, causing the arginine (R) at amino acid position 77 to be replaced by a proline (P). 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

0.13

BayesDel_addAF

Benign

-0.015

BayesDel_noAF

Benign

-0.26

CADD

Benign

1.8

DANN

Benign

0.77

DEOGEN2

Benign

0.089

T;T

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.60

.;T

M_CAP

Uncertain

0.26

MetaRNN

Benign

0.094

T;T

MetaSVM

Benign

-0.67

MutationAssessor

Benign

0.93

L;L

PrimateAI

Benign

0.22

PROVEAN

Uncertain

-3.5

D;D

REVEL

Benign

0.26

Sift

Uncertain

0.023

D;D

Sift4G

Benign

0.27

T;T

Polyphen

0.0030

B;B

Vest4

0.10

MutPred

0.37

Gain of catalytic residue at P76 (P = 0.0126);Gain of catalytic residue at P76 (P = 0.0126);

MVP

0.19

MPC

0.016

ClinPred

0.084

GERP RS

1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.32

gMVP

0.60

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over