NM_145102.4:c.552T>C

Variant names:

• chr7-99512590-T-C
• rs61735345
• NM_145102.4:c.552T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BS1 BS2

The NM_145102.4(ZKSCAN5):​c.552T>C​(p.Asn184Asn) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00241 in 1,613,522 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (17 hom., cov: 31)
  • Exomes 𝑓: 0.0015 (21 hom.)
• Consequence: ZKSCAN5 NM_145102.4 splice_region, synonymous
• Scores: Splicing: ADA: 0.0004359
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.233
• Publications: 3 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 7-99512590-T-C is Benign according to our data. Variant chr7-99512590-T-C is described in ClinVar as Benign. ClinVar VariationId is 780699.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.233 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0107 (1632/152046) while in subpopulation AFR AF = 0.0368 (1528/41470). AF 95% confidence interval is 0.0353. There are 17 homozygotes in GnomAd4. There are 781 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 17 AR gene

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.552T>C	p.Asn184Asn	splice_region synonymous	Exon 3 of 7	NP_659570.1	Q9Y2L8
	ZKSCAN5	NM_001318084.1		c.-105T>C		splice_region	Exon 2 of 5	NP_001305013.1	Q9Y2L8
	ZKSCAN5	NM_001318082.2		c.552T>C	p.Asn184Asn	splice_region synonymous	Exon 3 of 7	NP_001305011.1	Q9Y2L8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZKSCAN5	ENST00000326775.10	TSL:1 MANE Select	c.552T>C	p.Asn184Asn	splice_region synonymous	Exon 3 of 7	ENSP00000322872.5	Q9Y2L8
	ZKSCAN5	ENST00000394170.6	TSL:1	c.552T>C	p.Asn184Asn	splice_region synonymous	Exon 3 of 7	ENSP00000377725.2	Q9Y2L8
	ZKSCAN5	ENST00000451158.5	TSL:1	c.552T>C	p.Asn184Asn	splice_region synonymous	Exon 3 of 7	ENSP00000392104.1	Q9Y2L8

Frequencies

GnomAD3 genomes AF: 0.0107 AC: 1629 AN: 151928 Hom.: 17 Cov.: 31

Gnomad AFR AF: 0.0369

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00295

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000588

Gnomad OTH AF: 0.00574

GnomAD2 exomes AF: 0.00327 AC: 817 AN: 250070 AF XY: 0.00252

Gnomad AFR exome AF: 0.0383

Gnomad AMR exome AF: 0.00189

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000700

Gnomad OTH exome AF: 0.00180

GnomAD4 exome AF: 0.00155 AC: 2263 AN: 1461476 Hom.: 21 Cov.: 30 AF XY: 0.00141 AC XY: 1026 AN XY: 727056

African (AFR) AF: 0.0390 AC: 1305 AN: 33456

American (AMR) AF: 0.00211 AC: 94 AN: 44628

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39694

South Asian (SAS) AF: 0.00128 AC: 110 AN: 86226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00225 AC: 13 AN: 5766

European-Non Finnish (NFE) AF: 0.000530 AC: 589 AN: 1111830

Other (OTH) AF: 0.00250 AC: 151 AN: 60374

GnomAD4 genome AF: 0.0107 AC: 1632 AN: 152046 Hom.: 17 Cov.: 31 AF XY: 0.0105 AC XY: 781 AN XY: 74318

African (AFR) AF: 0.0368 AC: 1528 AN: 41470

American (AMR) AF: 0.00288 AC: 44 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5150

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000588 AC: 40 AN: 67972

Other (OTH) AF: 0.00568 AC: 12 AN: 2112

Alfa AF: 0.00442 Hom.: 15

Bravo AF: 0.0117

Asia WGS AF: 0.00433 AC: 15 AN: 3478

EpiCase AF: 0.000654

EpiControl AF: 0.00131

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	9.5
DANN	Benign	0.69
PhyloP100		-0.23
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=68/32	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00044
dbscSNV1_RF	Benign	0.090
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: rs61735345; hg19: chr7-99110213;