chr17-82831280-T-C

Position:

• chr17-82831280-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000269394.4(ZNF750):​c.1175A>G​(p.Gln392Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00744 in 1,613,872 control chromosomes in the GnomAD database, including 755 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.039 (404 hom., cov: 32)
  • Exomes 𝑓: 0.0041 (351 hom.)
• Consequence: ZNF750 ENST00000269394.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.741

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0024068952).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF750	NM_024702.3	c.1175A>G	p.Gln392Arg	missense_variant	2/3	ENST00000269394.4	NP_078978.2
TBCD	NM_005993.5	c.1318+16346T>C		intron_variant		ENST00000355528.9	NP_005984.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF750	ENST00000269394.4	c.1175A>G	p.Gln392Arg	missense_variant	2/3	1	NM_024702.3	ENSP00000269394	P1
TBCD	ENST00000355528.9	c.1318+16346T>C		intron_variant		1	NM_005993.5	ENSP00000347719	P1

Frequencies

GnomAD3 genomes AF: 0.0389 AC: 5923 AN: 152182 Hom.: 393 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0188

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000529

Gnomad OTH AF: 0.0268

GnomAD3 exomes AF: 0.00998 AC: 2505 AN: 251126 Hom.: 143 AF XY: 0.00693 AC XY: 941 AN XY: 135750

Gnomad AFR exome AF: 0.135

Gnomad AMR exome AF: 0.00642

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000392

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000396

Gnomad OTH exome AF: 0.00424

GnomAD4 exome AF: 0.00413 AC: 6032 AN: 1461572 Hom.: 351 Cov.: 35 AF XY: 0.00360 AC XY: 2614 AN XY: 727078

Gnomad4 AFR exome AF: 0.142

Gnomad4 AMR exome AF: 0.00747

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000441

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000297

Gnomad4 OTH exome AF: 0.00883

GnomAD4 genome AF: 0.0392 AC: 5971 AN: 152300 Hom.: 404 Cov.: 32 AF XY: 0.0385 AC XY: 2869 AN XY: 74464

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.0188

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000529

Gnomad4 OTH AF: 0.0265

Alfa AF: 0.00670 Hom.: 85

Bravo AF: 0.0448

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.131 AC: 578

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.0127 AC: 1547

Asia WGS AF: 0.0140 AC: 48 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000533

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.072	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.47	T
MetaRNN	Benign	0.0024	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
MutationTaster	Benign	8.3e-17	P;P;P;P;P
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.062
Sift	Benign	0.18	T
Sift4G	Benign	0.29	T
Polyphen		0.49	P
Vest4		0.040
MPC		0.24
ClinPred		0.0057	T
GERP RS		1.9
Varity_R		0.073
gMVP		0.22

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

Publications

LitVar

Other links and lift over

dbSNP: rs34687659; hg19: chr17-80789156; COSMIC: COSV53962300;