Genetic Variant NM_002114.4:c.356T>C (chr6-12120151-T-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_002114.4(HIVEP1):c.356T>C(p.Ile119Thr) 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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Consequence

HIVEP1
NM_002114.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.329

Publications

0 publications found

Variant links:

Genes affected

HIVEP1 (HGNC:4920): (HIVEP zinc finger 1) This gene encodes a transcription factor belonging to the ZAS family, members of which are large proteins that contain a ZAS domain - a modular protein structure consisting of a pair of C2H2 zinc fingers with an acidic-rich region and a serine/threonine-rich sequence. These proteins bind specifically to the DNA sequence motif, GGGACTTTCC, found in the enhancer elements of several viral promoters, including human immunodeficiency virus (HIV), and to related sequences found in the enhancer elements of a number of cellular promoters. This protein binds to this sequence motif, suggesting a role in the transcriptional regulation of both viral and cellular genes. [provided by RefSeq, Oct 2011]

HIVEP1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.019184083).

BP6

Variant 6-12120151-T-C is Benign according to our data. Variant chr6-12120151-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3525712.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002114.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HIVEP1	NM_002114.4	MANE Select	c.356T>C	p.Ile119Thr	missense	Exon 4 of 9	NP_002105.3	P15822-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HIVEP1	ENST00000379388.7	TSL:1 MANE Select	c.356T>C	p.Ile119Thr	missense	Exon 4 of 9	ENSP00000368698.2	P15822-1
HIVEP1	ENST00000714231.1		c.-251T>C		5_prime_UTR_premature_start_codon_gain	Exon 3 of 8	ENSP00000519512.1	A0AAQ5BHS1
HIVEP1	ENST00000714232.1		c.-251T>C		5_prime_UTR_premature_start_codon_gain	Exon 5 of 10	ENSP00000519513.1	A0AAQ5BHS1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.17

(source)

DANN

Benign

0.15

DEOGEN2

Benign

0.0066

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.099

LIST_S2

Benign

0.56

M_CAP

Benign

0.013

MetaRNN

Benign

0.019

MetaSVM

Benign

-0.89

PhyloP100

-0.33

PrimateAI

Benign

0.25

PROVEAN

Benign

1.7

REVEL

Benign

0.068

Sift

Benign

1.0

Sift4G

Benign

0.62

Vest4

0.014

MutPred

0.14

Gain of glycosylation at I119 (P = 0.0049)

MVP

0.14

MPC

0.11

ClinPred

0.022

GERP RS

-11

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.020

Mutation Taster

=96/4

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over