Variant 7-101218171-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006349.3(ZNHIT1):c.-25T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 1,610,718 control chromosomes in the GnomAD database, including 42,781 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4141 hom., cov: 32)

Exomes 𝑓: 0.23 ( 38640 hom. )

Consequence

ZNHIT1
NM_006349.3 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.42

Variant links:

Genes affected

ZNHIT1 (HGNC:21688): (zinc finger HIT-type containing 1) Predicted to enable histone deacetylase binding activity and nucleosome binding activity. Predicted to be involved in histone exchange. Predicted to act upstream of or within several processes, including negative regulation of G0 to G1 transition; negative regulation of transcription by RNA polymerase II; and regulation of histone deacetylation. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZNHIT1 links:

PLOD3 (HGNC:9083): (procollagen-lysine,2-oxoglutarate 5-dioxygenase 3) The protein encoded by this gene is a membrane-bound homodimeric enzyme that is localized to the cisternae of the rough endoplasmic reticulum. The enzyme (cofactors iron and ascorbate) catalyzes the hydroxylation of lysyl residues in collagen-like peptides. The resultant hydroxylysyl groups are attachment sites for carbohydrates in collagen and thus are critical for the stability of intermolecular crosslinks. Some patients with Ehlers-Danlos syndrome type VIB have deficiencies in lysyl hydroxylase activity. [provided by RefSeq, Jul 2008]

PLOD3 links:

ZNHIT1 (HGNC:):

ZNHIT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 7-101218171-T-C is Benign according to our data. Variant chr7-101218171-T-C is described in ClinVar as [Benign]. Clinvar id is 1267931.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNHIT1	NM_006349.3 linkuse as main transcript	c.-25T>C		5_prime_UTR_variant	1/5	ENST00000305105.3	NP_006340.1	O43257
ZNHIT1	XM_011515739.3 linkuse as main transcript	c.-248T>C		5_prime_UTR_variant	1/5		XP_011514041.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNHIT1	ENST00000305105 linkuse as main transcript	c.-25T>C		5_prime_UTR_variant	1/5	1	NM_006349.3	ENSP00000304593.2		O43257

Frequencies

GnomAD3 genomes

AF:

0.232

AC:

35253

AN:

152088

Hom.:

4133

Cov.:

show subpopulations

Gnomad AFR

AF:

0.230

Gnomad AMI

AF:

0.289

Gnomad AMR

AF:

0.251

Gnomad ASJ

AF:

0.305

Gnomad EAS

AF:

0.183

Gnomad SAS

AF:

0.284

Gnomad FIN

AF:

0.164

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.234

Gnomad OTH

AF:

0.265

GnomAD3 exomes

AF:

0.228

AC:

56865

AN:

249470

Hom.:

6649

AF XY:

0.233

AC XY:

31401

AN XY:

135050

show subpopulations

Gnomad AFR exome

AF:

0.229

Gnomad AMR exome

AF:

0.200

Gnomad ASJ exome

AF:

0.310

Gnomad EAS exome

AF:

0.183

Gnomad SAS exome

AF:

0.289

Gnomad FIN exome

AF:

0.160

Gnomad NFE exome

AF:

0.231

Gnomad OTH exome

AF:

0.256

GnomAD4 exome

AF:

0.229

AC:

333694

AN:

1458512

Hom.:

38640

Cov.:

AF XY:

0.230

AC XY:

166859

AN XY:

725336

show subpopulations

Gnomad4 AFR exome

AF:

0.231

Gnomad4 AMR exome

AF:

0.201

Gnomad4 ASJ exome

AF:

0.303

Gnomad4 EAS exome

AF:

0.173

Gnomad4 SAS exome

AF:

0.280

Gnomad4 FIN exome

AF:

0.166

Gnomad4 NFE exome

AF:

0.228

Gnomad4 OTH exome

AF:

0.239

GnomAD4 genome

AF:

0.232

AC:

35285

AN:

152206

Hom.:

4141

Cov.:

AF XY:

0.232

AC XY:

17230

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.231

Gnomad4 AMR

AF:

0.251

Gnomad4 ASJ

AF:

0.305

Gnomad4 EAS

AF:

0.183

Gnomad4 SAS

AF:

0.283

Gnomad4 FIN

AF:

0.164

Gnomad4 NFE

AF:

0.233

Gnomad4 OTH

AF:

0.262

Alfa

AF:

0.238

Hom.:

7540

Bravo

AF:

0.234

Asia WGS

AF:

0.250

AC:

873

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 19, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.8

DANN

Benign

0.52

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over