6-28434988-T-A

Position:

• chr6-28434988-T-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001012455.2(ZSCAN23):​c.647A>T​(p.Gln216Leu) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZSCAN23 NM_001012455.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.652

Genes affected

ZSCAN23 (HGNC:21193): (zinc finger and SCAN domain containing 23) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZSCAN23 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03450486).
• BP6: Variant 6-28434988-T-A is Benign according to our data. Variant chr6-28434988-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 2287310.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZSCAN23	NM_001012455.2	c.647A>T	p.Gln216Leu	missense_variant	4/4	ENST00000289788.5	NP_001012458.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZSCAN23	ENST00000289788.5	c.647A>T	p.Gln216Leu	missense_variant	4/4	1	NM_001012455.2	ENSP00000289788.4
ZSCAN23	ENST00000481983.5	n.*58A>T		non_coding_transcript_exon_variant	3/4	5		ENSP00000435430.1
ZSCAN23	ENST00000486481.1	n.343A>T		non_coding_transcript_exon_variant	3/3	2
ZSCAN23	ENST00000481983.5	n.*58A>T		3_prime_UTR_variant	3/4	5		ENSP00000435430.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 04, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.32
DANN	Benign	0.76
DEOGEN2	Benign	0.0028	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.00094	N
LIST_S2	Benign	0.090	T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-2.2	N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	3.1	N
REVEL	Benign	0.085
Sift	Benign	0.90	T
Sift4G	Benign	0.49	T
Polyphen		0.0	B
Vest4		0.053
MutPred		0.67		Loss of ubiquitination at K215 (P = 0.0368);
MVP		0.13
MPC		0.25
ClinPred		0.044	T
GERP RS		-2.4
Varity_R		0.045
gMVP		0.11

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: chr6-28402765;