7-99506177-A-G

Variant names:

• chr7-99506177-A-G
• rs370917462
• NM_145102.4:c.133A>G

Variant summary

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

The NM_145102.4(ZKSCAN5):​c.133A>G​(p.Thr45Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T45S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ZKSCAN5 NM_145102.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.930
• Publications: 0 publications found

Genes affected

ZKSCAN5 (HGNC:12867): (zinc finger with KRAB and SCAN domains 5) This gene encodes a zinc finger protein of the Kruppel family. The protein contains a SCAN box and a KRAB A domain and may be involved in transcriptional regulation. A similar protein in mouse is differentially expressed in spermatogenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

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=0.022961974).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145102.4. 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
	ZKSCAN5	NM_145102.4	MANE Select	c.133A>G	p.Thr45Ala	missense	Exon 2 of 7	NP_659570.1	Q9Y2L8
	ZKSCAN5	NM_001318082.2		c.133A>G	p.Thr45Ala	missense	Exon 2 of 7	NP_001305011.1	Q9Y2L8
	ZKSCAN5	NM_014569.4		c.133A>G	p.Thr45Ala	missense	Exon 2 of 7	NP_055384.1	Q9Y2L8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZKSCAN5	ENST00000326775.10	TSL:1 MANE Select	c.133A>G	p.Thr45Ala	missense	Exon 2 of 7	ENSP00000322872.5	Q9Y2L8
	ZKSCAN5	ENST00000394170.6	TSL:1	c.133A>G	p.Thr45Ala	missense	Exon 2 of 7	ENSP00000377725.2	Q9Y2L8
	ZKSCAN5	ENST00000451158.5	TSL:1	c.133A>G	p.Thr45Ala	missense	Exon 2 of 7	ENSP00000392104.1	Q9Y2L8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461894 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 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: 0.00000180 AC: 2 AN: 1112012

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.0
DANN	Benign	0.56
DEOGEN2	Benign	0.018	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0096	N
LIST_S2	Benign	0.043	T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.023	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.14	N
PhyloP100		-0.93
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.46	N
REVEL	Benign	0.0060
Sift	Benign	0.42	T
Sift4G	Benign	0.76	T
Polyphen		0.0	B
Vest4		0.079
MutPred		0.29		Loss of phosphorylation at T45 (P = 0.0514)
MVP		0.030
MPC		0.24
ClinPred		0.23	T
GERP RS		-6.3
Varity_R		0.031
gMVP		0.46
Mutation Taster		=100/0	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: rs370917462; hg19: chr7-99103800;