chr3-44557168-A-C

Variant names:

• chr3-44557168-A-C
• rs1699318399
• NM_001288590.2:c.121A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001288590.2(ZKSCAN7):​c.121A>C​(p.Ser41Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: ZKSCAN7 NM_001288590.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.367
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1480434).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001288590.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZKSCAN7	NM_001288590.2	MANE Select	c.121A>C	p.Ser41Arg	missense	Exon 2 of 6	NP_001275519.1	Q9P0L1-1
	ZKSCAN7	NM_018651.4		c.121A>C	p.Ser41Arg	missense	Exon 2 of 6	NP_061121.2
	ZKSCAN7	NM_001288591.2		c.121A>C	p.Ser41Arg	missense	Exon 2 of 6	NP_001275520.1	Q9P0L1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZKSCAN7	ENST00000426540.6	TSL:2 MANE Select	c.121A>C	p.Ser41Arg	missense	Exon 2 of 6	ENSP00000395524.1	Q9P0L1-1
	ZKSCAN7	ENST00000273320.7	TSL:1	c.121A>C	p.Ser41Arg	missense	Exon 2 of 6	ENSP00000273320.3	Q9P0L1-1
	ZKSCAN7	ENST00000341840.7	TSL:1	c.121A>C	p.Ser41Arg	missense	Exon 2 of 6	ENSP00000345404.3	Q9P0L1-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461892 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.094	T
Eigen	Benign	0.11
Eigen_PC	Benign	0.066
FATHMM_MKL	Benign	0.33	N
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.37
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.057
Sift	Uncertain	0.0070	D
Sift4G	Benign	0.069	T
Polyphen		0.74	P
Vest4		0.28
MutPred		0.31		Gain of MoRF binding (P = 0.0174)
MVP		0.47
MPC		0.32
ClinPred		0.71	D
GERP RS		4.5
Varity_R		0.12
gMVP		0.18
Mutation Taster		=88/12	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

dbSNP: rs1699318399; hg19: chr3-44598660;