NM_024702.3:c.1464T>A

Variant names:

• chr17-82830850-A-T
• rs35792712
• NM_024702.3:c.1464T>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_024702.3(ZNF750):​c.1464T>A​(p.Pro488Pro) variant causes a synonymous 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. Synonymous variant affecting the same amino acid position (i.e. P488P) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF750 NM_024702.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP7: Synonymous conserved (PhyloP=-1.43 with no splicing effect.

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.1464T>A	p.Pro488Pro	synonymous	Exon 3 of 3	NP_078978.2
	TBCD	NM_005993.5	MANE Select	c.1318+15916A>T		intron	N/A	NP_005984.3
	TBCD	NM_001411101.1		c.1267+15916A>T		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.1464T>A	p.Pro488Pro	synonymous	Exon 3 of 3	ENSP00000269394.3
	TBCD	ENST00000355528.9	TSL:1 MANE Select	c.1318+15916A>T		intron	N/A	ENSP00000347719.4
	ZNF750	ENST00000572562.1	TSL:2	c.267T>A	p.Pro89Pro	synonymous	Exon 3 of 3	ENSP00000458389.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.063
DANN	Benign	0.48
PhyloP100		-1.4
PromoterAI		-0.015	Neutral
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: rs35792712; hg19: chr17-80788726;