11-119127120-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2BP4_StrongBS2

The NM_198971.3(HINFP):​c.176C>T​(p.Pro59Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,456,970 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

HINFP
NM_198971.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.464
Variant links:
Genes affected
HINFP (HGNC:17850): (histone H4 transcription factor) This gene encodes a transcription factor that interacts with methyl-CpG-binding protein-2 (MBD2), a component of the MeCP1 histone deacetylase (HDAC) complex, and plays a role in DNA methylation and transcription repression. Alternatively spliced transcript variants have been found for this gene.[provided by RefSeq, Aug 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06292379).
BS2
High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HINFPNM_198971.3 linkc.176C>T p.Pro59Leu missense_variant Exon 2 of 10 ENST00000350777.7 NP_945322.1 Q9BQA5-1A0A024R3F5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HINFPENST00000350777.7 linkc.176C>T p.Pro59Leu missense_variant Exon 2 of 10 1 NM_198971.3 ENSP00000318085.3 Q9BQA5-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000816
AC:
2
AN:
245166
Hom.:
0
AF XY:
0.00000753
AC XY:
1
AN XY:
132792
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000591
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:
0.00000343
AC:
5
AN:
1456970
Hom.:
0
Cov.:
30
AF XY:
0.00000276
AC XY:
2
AN XY:
724798
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000113
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.:
33
Bravo
AF:
0.0000113

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Aug 05, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.176C>T (p.P59L) alteration is located in exon 3 (coding exon 1) of the HINFP gene. This alteration results from a C to T substitution at nucleotide position 176, causing the proline (P) at amino acid position 59 to be replaced by a leucine (L). 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
0.064
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
12
DANN
Benign
0.60
DEOGEN2
Benign
0.091
T;.;.
Eigen
Benign
-0.87
Eigen_PC
Benign
-0.89
FATHMM_MKL
Benign
0.13
N
LIST_S2
Benign
0.58
T;T;T
M_CAP
Benign
0.0072
T
MetaRNN
Benign
0.063
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
2.0
M;.;M
PrimateAI
Benign
0.35
T
PROVEAN
Benign
-0.35
N;N;N
REVEL
Benign
0.056
Sift
Benign
0.31
T;T;T
Sift4G
Benign
0.35
T;T;T
Polyphen
0.0
B;.;.
Vest4
0.30
MutPred
0.39
Loss of glycosylation at P59 (P = 0.0586);Loss of glycosylation at P59 (P = 0.0586);Loss of glycosylation at P59 (P = 0.0586);
MVP
0.25
MPC
0.47
ClinPred
0.027
T
GERP RS
0.25
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.053
gMVP
0.26

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: rs915472749; hg19: chr11-118997830; API