6-12120151-T-C

Variant names:

• chr6-12120151-T-C
• rs1775476480
• NM_002114.4:c.356T>C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_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. 14/19 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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.329

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]

ACMG classification

Verdict is Likely_benign. Variant got -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 id is 3525712.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HIVEP1	NM_002114.4	c.356T>C	p.Ile119Thr	missense_variant	Exon 4 of 9	ENST00000379388.7	NP_002105.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HIVEP1	ENST00000379388.7	c.356T>C	p.Ile119Thr	missense_variant	Exon 4 of 9	1	NM_002114.4	ENSP00000368698.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Dec 10, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.17
DANN	Benign	0.15
DEOGEN2	Benign	0.0066	.;T;.;.;T
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.099	N
LIST_S2	Benign	0.56	T;T;T;.;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.019	T;T;T;T;T
MetaSVM	Benign	-0.89	T
PrimateAI	Benign	0.25	T
PROVEAN	Benign	1.7	N;N;.;N;N
REVEL	Benign	0.068
Sift	Benign	1.0	T;T;.;T;T
Sift4G	Benign	0.62	T;T;T;T;T
Vest4		0.014, 0.013
MutPred		0.14		Gain of glycosylation at I119 (P = 0.0049);Gain of glycosylation at I119 (P = 0.0049);Gain of glycosylation at I119 (P = 0.0049);Gain of glycosylation at I119 (P = 0.0049);Gain of glycosylation at I119 (P = 0.0049);
MVP		0.14
MPC		0.11
ClinPred		0.022	T
GERP RS		-11
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.020

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

Other links and lift over

dbSNP: rs1775476480; hg19: chr6-12120384;