NM_024702.3:c.-112A>C

Variant names:

• chr17-82832566-T-G
• rs3744165
• NM_024702.3:c.-112A>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_024702.3(ZNF750):​c.-112A>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 0.823 in 943,716 control chromosomes in the GnomAD database, including 321,698 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.81 (49787 hom., cov: 33)
  • Exomes 𝑓: 0.83 (271911 hom.)
• Consequence: ZNF750 NM_024702.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.919
• Publications: 28 publications found

Genes affected

ZNF750 (HGNC:25843): (zinc finger protein 750) This gene encodes a protein with a nuclear localization site and a C2H2 zinc finger domain. Mutations in this gene have been associated with seborrhea-like dermatitis with psoriasiform elements. [provided by RefSeq, Jul 2008]

TBCD (HGNC:11581): (tubulin folding cofactor D) Cofactor D is one of four proteins (cofactors A, D, E, and C) involved in the pathway leading to correctly folded beta-tubulin from folding intermediates. Cofactors A and D are believed to play a role in capturing and stabilizing beta-tubulin intermediates in a quasi-native confirmation. Cofactor E binds to the cofactor D/beta-tubulin complex; interaction with cofactor C then causes the release of beta-tubulin polypeptides that are committed to the native state. [provided by RefSeq, Jul 2008]

TBCD Gene-Disease associations (from GenCC):

• early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 17-82832566-T-G is Benign according to our data. Variant chr17-82832566-T-G is described in ClinVar as [Benign]. Clinvar id is 1237571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.897 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF750	NM_024702.3	c.-112A>C		5_prime_UTR_variant	Exon 2 of 3	ENST00000269394.4	NP_078978.2
TBCD	NM_005993.5	c.1318+17632T>G		intron_variant	Intron 13 of 38	ENST00000355528.9	NP_005984.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF750	ENST00000269394.4	c.-112A>C		5_prime_UTR_variant	Exon 2 of 3	1	NM_024702.3	ENSP00000269394.3
TBCD	ENST00000355528.9	c.1318+17632T>G		intron_variant	Intron 13 of 38	1	NM_005993.5	ENSP00000347719.4

Frequencies

GnomAD3 genomes AF: 0.806 AC: 122565 AN: 152086 Hom.: 49752 Cov.: 33

Gnomad AFR AF: 0.719

Gnomad AMI AF: 0.848

Gnomad AMR AF: 0.884

Gnomad ASJ AF: 0.769

Gnomad EAS AF: 0.920

Gnomad SAS AF: 0.687

Gnomad FIN AF: 0.848

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.835

Gnomad OTH AF: 0.820

GnomAD4 exome AF: 0.826 AC: 654087 AN: 791512 Hom.: 271911 Cov.: 11 AF XY: 0.820 AC XY: 339552 AN XY: 414070

African (AFR) AF: 0.718 AC: 14718 AN: 20492

American (AMR) AF: 0.917 AC: 32420 AN: 35352

Ashkenazi Jewish (ASJ) AF: 0.767 AC: 16357 AN: 21322

East Asian (EAS) AF: 0.902 AC: 31153 AN: 34552

South Asian (SAS) AF: 0.685 AC: 46553 AN: 67946

European-Finnish (FIN) AF: 0.844 AC: 30279 AN: 35882

Middle Eastern (MID) AF: 0.757 AC: 2621 AN: 3464

European-Non Finnish (NFE) AF: 0.840 AC: 448534 AN: 534078

Other (OTH) AF: 0.819 AC: 31452 AN: 38424

GnomAD4 genome AF: 0.806 AC: 122659 AN: 152204 Hom.: 49787 Cov.: 33 AF XY: 0.806 AC XY: 60012 AN XY: 74426

African (AFR) AF: 0.719 AC: 29855 AN: 41512

American (AMR) AF: 0.885 AC: 13534 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.769 AC: 2669 AN: 3472

East Asian (EAS) AF: 0.919 AC: 4740 AN: 5158

South Asian (SAS) AF: 0.687 AC: 3311 AN: 4822

European-Finnish (FIN) AF: 0.848 AC: 8994 AN: 10608

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.835 AC: 56823 AN: 68020

Other (OTH) AF: 0.822 AC: 1734 AN: 2110

Alfa AF: 0.828 Hom.: 96402

Bravo AF: 0.808

Asia WGS AF: 0.792 AC: 2758 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 13, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.3
DANN	Benign	0.64
PhyloP100		0.92
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=153/147	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3744165; hg19: chr17-80790442;