X-153420249-A-T

Variant names:

• chrX-153420249-A-T
• NM_001136273.2:c.182A>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001136273.2(ZFP92):​c.182A>T​(p.His61Leu) variant causes a missense 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. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 24)
• Consequence: ZFP92 NM_001136273.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.625

Genes affected

ZFP92 (HGNC:12865): (ZFP92 zinc finger protein) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03935179).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFP92	NM_001136273.2	c.182A>T	p.His61Leu	missense_variant	Exon 5 of 6	ENST00000338647.7	NP_001129745.1
ZFP92	NM_001386944.1	c.182A>T	p.His61Leu	missense_variant	Exon 4 of 5		NP_001373873.1
ZFP92	NM_001386945.1	c.182A>T	p.His61Leu	missense_variant	Exon 6 of 7		NP_001373874.1
ZFP92	NM_001386943.1	c.56A>T	p.His19Leu	missense_variant	Exon 3 of 4		NP_001373872.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFP92	ENST00000338647.7	c.182A>T	p.His61Leu	missense_variant	Exon 5 of 6	5	NM_001136273.2	ENSP00000462054.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 24

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.182A>T (p.H61L) alteration is located in exon 3 (coding exon 3) of the ZFP92 gene. This alteration results from a A to T substitution at nucleotide position 182, causing the histidine (H) at amino acid position 61 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	14
DANN	Benign	0.92
DEOGEN2	Benign	0.078	T
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.10	T
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.039	T
MutationAssessor	Benign	0.25	N
PrimateAI	Benign	0.34	T
Sift4G	Benign	0.17	T
Polyphen		0.24	B
Vest4		0.21
MVP		0.29
MPC		1.3
GERP RS		0.64
Varity_R		0.17
gMVP		0.14

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-152685707;