chr17-82831393-G-A

Variant names:

• chr17-82831393-G-A
• rs34188981
• NM_024702.3:c.1062C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_024702.3(ZNF750):​c.1062C>T​(p.Thr354Thr) 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.02
• Publications: 7 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 -21 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 VariationId is 1290639.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF750	NM_024702.3	MANE Select	c.1062C>T	p.Thr354Thr	synonymous	Exon 2 of 3	NP_078978.2
	TBCD	NM_005993.5	MANE Select	c.1318+16459G>A		intron	N/A	NP_005984.3
	TBCD	NM_001411101.1		c.1267+16459G>A		intron	N/A	NP_001398030.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF750	ENST00000269394.4	TSL:1 MANE Select	c.1062C>T	p.Thr354Thr	synonymous	Exon 2 of 3	ENSP00000269394.3
	TBCD	ENST00000355528.9	TSL:1 MANE Select	c.1318+16459G>A		intron	N/A	ENSP00000347719.4
	ZNF750	ENST00000572562.1	TSL:2	c.-136C>T		5_prime_UTR	Exon 2 of 3	ENSP00000458389.1

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

GnomAD2 exomes AF: 0.0224 AC: 5635 AN: 251456 AF XY: 0.0209

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 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

African (AFR) AF: 0.111 AC: 3710 AN: 33480

American (AMR) AF: 0.0114 AC: 510 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00960 AC: 251 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0159 AC: 1375 AN: 86258

European-Finnish (FIN) AF: 0.00680 AC: 363 AN: 53408

Middle Eastern (MID) AF: 0.0121 AC: 70 AN: 5768

European-Non Finnish (NFE) AF: 0.0217 AC: 24142 AN: 1112010

Other (OTH) AF: 0.0223 AC: 1348 AN: 60396

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

African (AFR) AF: 0.105 AC: 4357 AN: 41522

American (AMR) AF: 0.0183 AC: 279 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00922 AC: 32 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.0126 AC: 61 AN: 4824

European-Finnish (FIN) AF: 0.00377 AC: 40 AN: 10614

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0211 AC: 1437 AN: 68018

Other (OTH) AF: 0.0298 AC: 63 AN: 2112

Alfa AF: 0.0256 Hom.: 184

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.8
DANN	Benign	0.76
PhyloP100		1.0
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs34188981; hg19: chr17-80789269;