rs186016810

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001012754.4(NHLRC3):​c.320C>G​(p.Pro107Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,998 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P107L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

NHLRC3
NM_001012754.4 missense

Scores

10
7
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.74
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 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.875

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NHLRC3NM_001012754.4 linkc.320C>G p.Pro107Arg missense_variant Exon 3 of 7 ENST00000379600.8 NP_001012772.1 Q5JS37-1Q68DP7
NHLRC3NM_001017370.3 linkc.320C>G p.Pro107Arg missense_variant Exon 3 of 6 NP_001017370.1 Q5JS37-2Q68DP7
NHLRC3NR_073109.1 linkn.391C>G non_coding_transcript_exon_variant Exon 3 of 7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NHLRC3ENST00000379600.8 linkc.320C>G p.Pro107Arg missense_variant Exon 3 of 7 1 NM_001012754.4 ENSP00000368920.3 Q5JS37-1
NHLRC3ENST00000379599.6 linkc.320C>G p.Pro107Arg missense_variant Exon 3 of 6 1 ENSP00000368919.2 Q5JS37-2
NHLRC3ENST00000470258 linkc.-272C>G 5_prime_UTR_variant Exon 3 of 7 1 ENSP00000418127.1 C9J973
NHLRC3ENST00000473371.1 linkn.1066C>G non_coding_transcript_exon_variant Exon 2 of 2 2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1459998
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
726456
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.96
BayesDel_addAF
Pathogenic
0.35
D
BayesDel_noAF
Pathogenic
0.27
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Benign
0.36
T;.
Eigen
Pathogenic
0.88
Eigen_PC
Pathogenic
0.83
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.91
D;D
M_CAP
Uncertain
0.16
D
MetaRNN
Pathogenic
0.87
D;D
MetaSVM
Pathogenic
0.98
D
MutationAssessor
Pathogenic
3.4
M;M
PrimateAI
Uncertain
0.60
T
PROVEAN
Pathogenic
-5.5
D;D
REVEL
Pathogenic
0.89
Sift
Uncertain
0.0040
D;D
Sift4G
Uncertain
0.0070
D;T
Polyphen
1.0
D;.
Vest4
0.75
MutPred
0.72
Gain of catalytic residue at F111 (P = 0.001);Gain of catalytic residue at F111 (P = 0.001);
MVP
0.98
MPC
0.44
ClinPred
1.0
D
GERP RS
5.4
Varity_R
0.62
gMVP
0.91

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: chr13-39613783; COSMIC: COSV61488448; COSMIC: COSV61488448; API