11-7038730-T-G

Variant names:

• chr11-7038730-T-G
• NM_176822.4:c.144T>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_176822.4(NLRP14):​c.144T>G​(p.Asn48Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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. N48T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NLRP14 NM_176822.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.595

Genes affected

NLRP14 (HGNC:22939): (NLR family pyrin domain containing 14) The protein encoded by this gene belongs to the NALP protein family. Members of the NALP protein family typically contain a NACHT domain, a NACHT-associated domain (NAD), a C-terminal leucine-rich repeat (LRR) region, and an N-terminal pyrin domain (PYD). This protein may play a regulatory role in the innate immune system as similar family members belong to the signal-induced multiprotein complex, the inflammasome, that activates the pro-inflammatory caspases, caspase-1 and caspase-5. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.045072168).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NLRP14	NM_176822.4	c.144T>G	p.Asn48Lys	missense_variant	Exon 2 of 12	ENST00000299481.5	NP_789792.1
NLRP14	XM_011520044.2	c.144T>G	p.Asn48Lys	missense_variant	Exon 2 of 11		XP_011518346.1
NLRP14	XM_047426867.1	c.144T>G	p.Asn48Lys	missense_variant	Exon 2 of 11		XP_047282823.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NLRP14	ENST00000299481.5	c.144T>G	p.Asn48Lys	missense_variant	Exon 2 of 12	5	NM_176822.4	ENSP00000299481.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.144T>G (p.N48K) alteration is located in exon 2 (coding exon 1) of the NLRP14 gene. This alteration results from a T to G substitution at nucleotide position 144, causing the asparagine (N) at amino acid position 48 to be replaced by a lysine (K). 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	0.091
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.7
DANN	Benign	0.97
DEOGEN2	Benign	0.0073	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.045	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.69	N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.38	N
REVEL	Benign	0.033
Sift	Benign	0.17	T
Sift4G	Benign	0.064	T
Polyphen		0.0090	B
Vest4		0.13
MutPred		0.54		Loss of ubiquitination at K52 (P = 0.0248);
MVP		0.21
MPC		0.019
ClinPred		0.065	T
GERP RS		1.8
Varity_R		0.19
gMVP		0.18

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: chr11-7059961;