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GeneBe

2-200897076-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001369441.2(NIF3L1):c.727C>T(p.Pro243Ser) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000000684 in 1,461,310 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

NIF3L1
NM_001369441.2 missense, splice_region

Scores

2
6
10
Splicing: ADA: 0.9890
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.17
Variant links:
Genes affected
NIF3L1 (HGNC:13390): (NGG1 interacting factor 3 like 1) Enables identical protein binding activity. Involved in positive regulation of transcription, DNA-templated. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NIF3L1NM_001369441.2 linkuse as main transcriptc.727C>T p.Pro243Ser missense_variant, splice_region_variant 5/7 ENST00000409020.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NIF3L1ENST00000409020.6 linkuse as main transcriptc.727C>T p.Pro243Ser missense_variant, splice_region_variant 5/75 NM_001369441.2 P1Q9GZT8-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000402
AC:
1
AN:
248702
Hom.:
0
AF XY:
0.00000741
AC XY:
1
AN XY:
134928
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000291
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461310
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
726974
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
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
Alfa
AF:
0.0000936
Hom.:
0
Bravo
AF:
0.00000378

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 submitterclinical testingAmbry GeneticsJul 09, 2021The c.727C>T (p.P243S) alteration is located in exon 5 (coding exon 4) of the NIF3L1 gene. This alteration results from a C to T substitution at nucleotide position 727, causing the proline (P) at amino acid position 243 to be replaced by a serine (S). 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
0.34
BayesDel_addAF
Benign
-0.038
T
BayesDel_noAF
Benign
-0.21
Cadd
Uncertain
24
Dann
Pathogenic
1.0
DEOGEN2
Benign
0.13
T;.;T
Eigen
Uncertain
0.22
Eigen_PC
Uncertain
0.39
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.90
D;D;.
M_CAP
Benign
0.039
D
MetaRNN
Uncertain
0.55
D;D;D
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Benign
0.48
T
PROVEAN
Uncertain
-3.3
D;D;D
REVEL
Benign
0.20
Sift
Benign
0.093
T;T;T
Sift4G
Benign
0.33
T;T;T
Polyphen
0.20
B;.;B
Vest4
0.69
MutPred
0.38
Loss of loop (P = 0.0804);.;Loss of loop (P = 0.0804);
MVP
0.36
MPC
0.26
ClinPred
0.75
D
GERP RS
6.0
Varity_R
0.38

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
0.99
dbscSNV1_RF
Pathogenic
0.86
SpliceAI score (max)
0.12
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: rs1424839923; hg19: chr2-201761799; API