rs3744165

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr17-82832566-T-A
• chr17-82832566-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024702.3(ZNF750):​c.-112A>T variant causes a 5 prime UTR 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF750 NM_024702.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF750	NM_024702.3	c.-112A>T		5_prime_UTR_variant	Exon 2 of 3	ENST00000269394.4	NP_078978.2
TBCD	NM_005993.5	c.1318+17632T>A		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>T		5_prime_UTR_variant	Exon 2 of 3	1	NM_024702.3	ENSP00000269394.3
TBCD	ENST00000355528.9	c.1318+17632T>A		intron_variant	Intron 13 of 38	1	NM_005993.5	ENSP00000347719.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 792212 Hom.: 0 Cov.: 11 AF XY: 0.00 AC XY: 0 AN XY: 414404

African (AFR) AF: 0.00 AC: 0 AN: 20510

American (AMR) AF: 0.00 AC: 0 AN: 35360

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21338

East Asian (EAS) AF: 0.00 AC: 0 AN: 34560

South Asian (SAS) AF: 0.00 AC: 0 AN: 67982

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35890

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3468

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 534650

Other (OTH) AF: 0.00 AC: 0 AN: 38454

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 96402

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.2
DANN	Benign	0.55
PhyloP100		0.92
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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

Other links and lift over

dbSNP: rs3744165; hg19: chr17-80790442;