13-39042267-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The ENST00000470258(NHLRC3):​c.-44A>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

NHLRC3
ENST00000470258 5_prime_UTR_premature_start_codon_gain

Scores

7
7
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.29
Variant links:
Genes affected
NHLRC3 (HGNC:33751): (NHL repeat containing 3) This gene encodes a protein containing NCL-1, HT2A and Lin-41 (NHL) family repeats. Mammalian NHL-repeat containing proteins may be involved in a variety of enzymatic processes, including protein modification through ubiquitination. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Aug 2012]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.808

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NHLRC3NM_001012754.4 linkc.548A>T p.Asp183Val missense_variant Exon 4 of 7 ENST00000379600.8 NP_001012772.1 Q5JS37-1Q68DP7
NHLRC3NM_001017370.3 linkc.386-1823A>T intron_variant Intron 3 of 5 NP_001017370.1 Q5JS37-2Q68DP7
NHLRC3NR_073109.1 linkn.619A>T non_coding_transcript_exon_variant Exon 4 of 7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NHLRC3ENST00000379600.8 linkc.548A>T p.Asp183Val missense_variant Exon 4 of 7 1 NM_001012754.4 ENSP00000368920.3 Q5JS37-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
27
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 19, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.548A>T (p.D183V) alteration is located in exon 4 (coding exon 4) of the NHLRC3 gene. This alteration results from a A to T substitution at nucleotide position 548, causing the aspartic acid (D) at amino acid position 183 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
Pathogenic
0.95
BayesDel_addAF
Pathogenic
0.25
D
BayesDel_noAF
Uncertain
0.12
CADD
Pathogenic
27
DANN
Uncertain
0.99
DEOGEN2
Benign
0.058
T
Eigen
Pathogenic
0.79
Eigen_PC
Pathogenic
0.77
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.92
D
M_CAP
Benign
0.067
D
MetaRNN
Pathogenic
0.81
D
MetaSVM
Benign
-0.56
T
MutationAssessor
Uncertain
2.2
M
PrimateAI
Uncertain
0.70
T
PROVEAN
Uncertain
-3.3
D
REVEL
Uncertain
0.54
Sift
Benign
0.034
D
Sift4G
Pathogenic
0.0010
D
Polyphen
1.0
D
Vest4
0.78
MutPred
0.49
Gain of catalytic residue at D181 (P = 6e-04);
MVP
0.79
MPC
0.51
ClinPred
1.0
D
GERP RS
5.4
Varity_R
0.36
gMVP
0.88

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs966518567; hg19: chr13-39616404; API