rs12450046

Variant names:

• chr17-82832512-G-A
• rs12450046
• NM_024702.3:c.-58C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-82832512-G-A
• chr17-82832512-G-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.-58C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 1,487,512 control chromosomes in the GnomAD database, including 22,965 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2308 hom., cov: 32)
  • Exomes 𝑓: 0.17 (20657 hom.)
• Consequence: ZNF750 NM_024702.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.497
• Publications: 12 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: ClinGen, PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 17-82832512-G-A is Benign according to our data. Variant chr17-82832512-G-A is described in ClinVar as Benign. ClinVar VariationId is 1227535.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024702.3. 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
	ZNF750	NM_024702.3	MANE Select	c.-58C>T		5_prime_UTR	Exon 2 of 3	NP_078978.2	Q32MQ0
	TBCD	NM_005993.5	MANE Select	c.1318+17578G>A		intron	N/A	NP_005984.3
	TBCD	NM_001411101.1		c.1267+17578G>A		intron	N/A	NP_001398030.1	A0A804HLI2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF750	ENST00000269394.4	TSL:1 MANE Select	c.-58C>T		5_prime_UTR	Exon 2 of 3	ENSP00000269394.3	Q32MQ0
	TBCD	ENST00000355528.9	TSL:1 MANE Select	c.1318+17578G>A		intron	N/A	ENSP00000347719.4	Q9BTW9-1
	TBCD	ENST00000684760.1		c.1318+17578G>A		intron	N/A	ENSP00000507696.1	A0A804HJY5

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25405 AN: 151974 Hom.: 2305 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.0822

Gnomad SAS AF: 0.0428

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.150

GnomAD4 exome AF: 0.169 AC: 226190 AN: 1335420 Hom.: 20657 Cov.: 21 AF XY: 0.165 AC XY: 110900 AN XY: 670752

African (AFR) AF: 0.129 AC: 4009 AN: 31112

American (AMR) AF: 0.284 AC: 12467 AN: 43860

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 3485 AN: 25384

East Asian (EAS) AF: 0.0736 AC: 2881 AN: 39130

South Asian (SAS) AF: 0.0511 AC: 4277 AN: 83680

European-Finnish (FIN) AF: 0.229 AC: 9163 AN: 40096

Middle Eastern (MID) AF: 0.0995 AC: 552 AN: 5546

European-Non Finnish (NFE) AF: 0.178 AC: 180183 AN: 1010066

Other (OTH) AF: 0.162 AC: 9173 AN: 56546

GnomAD4 genome AF: 0.167 AC: 25426 AN: 152092 Hom.: 2308 Cov.: 32 AF XY: 0.167 AC XY: 12411 AN XY: 74358

African (AFR) AF: 0.131 AC: 5426 AN: 41468

American (AMR) AF: 0.230 AC: 3510 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 494 AN: 3466

East Asian (EAS) AF: 0.0824 AC: 427 AN: 5184

South Asian (SAS) AF: 0.0427 AC: 206 AN: 4828

European-Finnish (FIN) AF: 0.231 AC: 2447 AN: 10580

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.182 AC: 12356 AN: 67974

Other (OTH) AF: 0.148 AC: 312 AN: 2108

Alfa AF: 0.173 Hom.: 3135

Bravo AF: 0.168

Asia WGS AF: 0.0600 AC: 210 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.7
DANN	Benign	0.83
PhyloP100		0.50
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs12450046; hg19: chr17-80790388; COSMIC: COSV53960652;