rs34188981

chr17-82831393-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_024702.3(ZNF750):c.1062C>T(p.Thr354=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0236 in 1,614,108 control chromosomes in the GnomAD database, including 789 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.041 (247 hom., cov: 32)
  • Exomes 𝑓: 0.022 (542 hom.)
• Consequence: ZNF750 NM_024702.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.02

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]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 17-82831393-G-A is Benign according to our data. Variant chr17-82831393-G-A is described in ClinVar as [Benign]. Clinvar id is 1290639.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.02 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF750	NM_024702.3	c.1062C>T	p.Thr354=	synonymous_variant	2/3	ENST00000269394.4
TBCD	NM_005993.5	c.1318+16459G>A		intron_variant		ENST00000355528.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF750	ENST00000269394.4	c.1062C>T	p.Thr354=	synonymous_variant	2/3	1	NM_024702.3	P1
TBCD	ENST00000355528.9	c.1318+16459G>A		intron_variant		1	NM_005993.5	P1

Frequencies

GnomAD3 genomes AF: 0.0414 AC: 6298 AN: 152110 Hom.: 248 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0183

Gnomad ASJ AF: 0.00922

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0126

Gnomad FIN AF: 0.00377

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0212

Gnomad OTH AF: 0.0301

GnomAD3 exomes AF: 0.0224 AC: 5635 AN: 251456 Hom.: 151 AF XY: 0.0209 AC XY: 2839 AN XY: 135918

Gnomad AFR exome AF: 0.113

Gnomad AMR exome AF: 0.0105

Gnomad ASJ exome AF: 0.00923

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0160

Gnomad FIN exome AF: 0.00591

Gnomad NFE exome AF: 0.0230

Gnomad OTH exome AF: 0.0178

GnomAD4 exome AF: 0.0217 AC: 31770 AN: 1461880 Hom.: 542 Cov.: 36 AF XY: 0.0211 AC XY: 15366 AN XY: 727244

Gnomad4 AFR exome AF: 0.111

Gnomad4 AMR exome AF: 0.0114

Gnomad4 ASJ exome AF: 0.00960

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0159

Gnomad4 FIN exome AF: 0.00680

Gnomad4 NFE exome AF: 0.0217

Gnomad4 OTH exome AF: 0.0223

GnomAD4 genome AF: 0.0414 AC: 6298 AN: 152228 Hom.: 247 Cov.: 32 AF XY: 0.0396 AC XY: 2949 AN XY: 74432

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.0183

Gnomad4 ASJ AF: 0.00922

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0126

Gnomad4 FIN AF: 0.00377

Gnomad4 NFE AF: 0.0211

Gnomad4 OTH AF: 0.0298

Alfa AF: 0.0290 Hom.: 72

Bravo AF: 0.0451

Asia WGS AF: 0.00751 AC: 26 AN: 3478

EpiCase AF: 0.0182

EpiControl AF: 0.0184

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	1.8
Dann	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs34188981; hg19: chr17-80789269;