NM_145102.4:c.444G>A

Variant names:

• chr7-99512482-G-A
• rs61739592
• NM_145102.4:c.444G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_145102.4(ZKSCAN5):​c.444G>A​(p.Arg148Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00237 in 1,613,796 control chromosomes in the GnomAD database, including 68 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (38 hom., cov: 31)
  • Exomes 𝑓: 0.0013 (30 hom.)
• Consequence: ZKSCAN5 NM_145102.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.42
• Publications: 2 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 7-99512482-G-A is Benign according to our data. Variant chr7-99512482-G-A is described in ClinVar as Benign. ClinVar VariationId is 783500.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.42 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0128 (1948/152276) while in subpopulation AFR AF = 0.0444 (1846/41542). AF 95% confidence interval is 0.0427. There are 38 homozygotes in GnomAd4. There are 950 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 38 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.444G>A	p.Arg148Arg	synonymous	Exon 3 of 7	NP_659570.1	Q9Y2L8
	ZKSCAN5	NM_001318082.2		c.444G>A	p.Arg148Arg	synonymous	Exon 3 of 7	NP_001305011.1	Q9Y2L8
	ZKSCAN5	NM_014569.4		c.444G>A	p.Arg148Arg	synonymous	Exon 3 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.444G>A	p.Arg148Arg	synonymous	Exon 3 of 7	ENSP00000322872.5	Q9Y2L8
	ZKSCAN5	ENST00000394170.6	TSL:1	c.444G>A	p.Arg148Arg	synonymous	Exon 3 of 7	ENSP00000377725.2	Q9Y2L8
	ZKSCAN5	ENST00000451158.5	TSL:1	c.444G>A	p.Arg148Arg	synonymous	Exon 3 of 7	ENSP00000392104.1	Q9Y2L8

Frequencies

GnomAD3 genomes AF: 0.0128 AC: 1948 AN: 152158 Hom.: 38 Cov.: 31

Gnomad AFR AF: 0.0446

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00504

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.0100

GnomAD2 exomes AF: 0.00344 AC: 864 AN: 250874 AF XY: 0.00240

Gnomad AFR exome AF: 0.0465

Gnomad AMR exome AF: 0.00264

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000123

Gnomad OTH exome AF: 0.000655

GnomAD4 exome AF: 0.00129 AC: 1881 AN: 1461520 Hom.: 30 Cov.: 30 AF XY: 0.00110 AC XY: 801 AN XY: 727086

African (AFR) AF: 0.0448 AC: 1499 AN: 33452

American (AMR) AF: 0.00284 AC: 127 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00312 AC: 18 AN: 5768

European-Non Finnish (NFE) AF: 0.0000612 AC: 68 AN: 1111812

Other (OTH) AF: 0.00273 AC: 165 AN: 60376

GnomAD4 genome AF: 0.0128 AC: 1948 AN: 152276 Hom.: 38 Cov.: 31 AF XY: 0.0128 AC XY: 950 AN XY: 74454

African (AFR) AF: 0.0444 AC: 1846 AN: 41542

American (AMR) AF: 0.00504 AC: 77 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68026

Other (OTH) AF: 0.00993 AC: 21 AN: 2114

Alfa AF: 0.00556 Hom.: 8

Bravo AF: 0.0145

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	12
DANN	Benign	0.66
PhyloP100		2.4
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs61739592; hg19: chr7-99110105;