NM_001288590.2:c.739A>G

Variant names:

• chr3-44568361-A-G
• rs143669519
• NM_001288590.2:c.739A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001288590.2(ZKSCAN7):​c.739A>G​(p.Ser247Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000737 in 1,613,976 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000077 (0 hom.)
• Consequence: ZKSCAN7 NM_001288590.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.13
• Publications: 2 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0412125).
• BP6: Variant 3-44568361-A-G is Benign according to our data. Variant chr3-44568361-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3334769.Status of the report is criteria_provided_single_submitter, 1 stars.

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.739A>G	p.Ser247Gly	missense	Exon 5 of 6	NP_001275519.1	Q9P0L1-1
	ZKSCAN7	NM_018651.4		c.739A>G	p.Ser247Gly	missense	Exon 5 of 6	NP_061121.2
	ZKSCAN7	NM_001288592.2		c.289A>G	p.Ser97Gly	missense	Exon 4 of 6	NP_001275521.1	C9J6L6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZKSCAN7	ENST00000426540.6	TSL:2 MANE Select	c.739A>G	p.Ser247Gly	missense	Exon 5 of 6	ENSP00000395524.1	Q9P0L1-1
	ZKSCAN7	ENST00000273320.7	TSL:1	c.739A>G	p.Ser247Gly	missense	Exon 5 of 6	ENSP00000273320.3	Q9P0L1-1
	ZKSCAN7	ENST00000447279.2	TSL:1	c.289A>G	p.Ser97Gly	missense	Exon 4 of 6	ENSP00000405034.1	C9J6L6

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152216 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000438 AC: 11 AN: 251350 AF XY: 0.0000221

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000968

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000773 AC: 113 AN: 1461760 Hom.: 0 Cov.: 31 AF XY: 0.0000729 AC XY: 53 AN XY: 727186

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000299 AC: 1 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

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

European-Non Finnish (NFE) AF: 0.0000962 AC: 107 AN: 1111910

Other (OTH) AF: 0.0000828 AC: 5 AN: 60392

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152216 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74366

African (AFR) AF: 0.0000241 AC: 1 AN: 41456

American (AMR) AF: 0.00 AC: 0 AN: 15282

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.000141 Hom.: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000247 AC: 3

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.062
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.64
DANN	Benign	0.58
DEOGEN2	Benign	0.038	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0019	N
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	-0.41	N
PhyloP100		-1.1
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.53	N
REVEL	Benign	0.010
Sift	Benign	0.29	T
Sift4G	Benign	0.44	T
Polyphen		0.0	B
Vest4		0.12
MVP		0.048
MPC		0.061
ClinPred		0.044	T
GERP RS		-0.29
Varity_R		0.030
gMVP		0.027
Mutation Taster		=98/2	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: rs143669519; hg19: chr3-44609853;