7-99519889-C-T

Variant names:

• chr7-99519889-C-T
• rs1801447283
• NM_145102.4:c.616C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_145102.4(ZKSCAN5):​c.616C>T​(p.Leu206Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZKSCAN5 NM_145102.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.236

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0697).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZKSCAN5	NM_145102.4	c.616C>T	p.Leu206Phe	missense_variant	Exon 4 of 7	ENST00000326775.10	NP_659570.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZKSCAN5	ENST00000326775.10	c.616C>T	p.Leu206Phe	missense_variant	Exon 4 of 7	1	NM_145102.4	ENSP00000322872.5
ZKSCAN5	ENST00000394170.6	c.616C>T	p.Leu206Phe	missense_variant	Exon 4 of 7	1		ENSP00000377725.2
ZKSCAN5	ENST00000451158.5	c.616C>T	p.Leu206Phe	missense_variant	Exon 4 of 7	1		ENSP00000392104.1
ZKSCAN5	ENST00000454175.1	n.616C>T		non_coding_transcript_exon_variant	Exon 3 of 5	1		ENSP00000405716.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461858 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727228

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 27, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.616C>T (p.L206F) alteration is located in exon 4 (coding exon 3) of the ZKSCAN5 gene. This alteration results from a C to T substitution at nucleotide position 616, causing the leucine (L) at amino acid position 206 to be replaced by a phenylalanine (F). 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	0.16
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.047	T;T;T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.063
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.64	.;.;T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.070	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M;M;M
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.97	N;N;N
REVEL	Benign	0.025
Sift	Benign	0.071	T;T;T
Sift4G	Benign	0.29	T;T;T
Polyphen		0.054	B;B;B
Vest4		0.21
MutPred		0.34		Gain of catalytic residue at L206 (P = 0.0184);Gain of catalytic residue at L206 (P = 0.0184);Gain of catalytic residue at L206 (P = 0.0184);
MVP		0.25
MPC		0.31
ClinPred		0.31	T
GERP RS		3.8
Varity_R		0.066
gMVP		0.068

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1801447283; hg19: chr7-99117512;