3-44565598-G-A

Variant names:

• chr3-44565598-G-A
• NM_001288590.2:c.535G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001288590.2(ZKSCAN7):​c.535G>A​(p.Ala179Thr) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZKSCAN7 NM_001288590.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.69
• Publications: 0 publications found

Genes affected

ZKSCAN7 (HGNC:12955): (zinc finger with KRAB and SCAN domains 7) 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]

ZKSCAN7-AS1 (HGNC:53964): (ZKSCAN7 ZNF cluster antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05723697).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZKSCAN7	NM_001288590.2	c.535G>A	p.Ala179Thr	missense_variant	Exon 3 of 6	ENST00000426540.6	NP_001275519.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZKSCAN7	ENST00000426540.6	c.535G>A	p.Ala179Thr	missense_variant	Exon 3 of 6	2	NM_001288590.2	ENSP00000395524.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.535G>A (p.A179T) alteration is located in exon 3 (coding exon 2) of the ZKSCAN7 gene. This alteration results from a G to A substitution at nucleotide position 535, causing the alanine (A) at amino acid position 179 to be replaced by a threonine (T). 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	0.070
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	6.2
DANN	Benign	0.69
DEOGEN2	Benign	0.073	T;.;.;T;T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.027	N
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.057	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;L;L;L;.;.
PhyloP100		1.7
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.44	N;N;N;N;N;N
REVEL	Benign	0.028
Sift	Benign	0.56	T;T;T;T;T;T
Sift4G	Benign	0.63	T;T;T;T;T;T
Polyphen		0.0030	B;B;B;B;.;.
Vest4		0.049
MutPred		0.25		Gain of glycosylation at A179 (P = 0.0078);Gain of glycosylation at A179 (P = 0.0078);Gain of glycosylation at A179 (P = 0.0078);Gain of glycosylation at A179 (P = 0.0078);.;.;
MVP		0.25
MPC		0.065
ClinPred		0.043	T
GERP RS		0.59
PromoterAI		-0.0088	Neutral
Varity_R		0.023
gMVP		0.13
Mutation Taster		=97/3	polymorphism

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

hg19: chr3-44607090;