NM_007137.5:c.147A>G

Variant names:

• chrX-47888091-A-G
• rs782661971
• NM_007137.5:c.147A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_007137.5(ZNF81):​c.147A>G​(p.Val49Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000132 in 1,208,069 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 75 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.000090 (0 hom., 2 hem., cov: 22)
  • Exomes 𝑓: 0.00014 (0 hom. 73 hem.)
• Consequence: ZNF81 NM_007137.5 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.126
• Publications: 0 publications found

Genes affected

ZNF81 (HGNC:13156): (zinc finger protein 81) This gene encodes a protein that likely functions as a transcription factor. The protein contains an N-terminal KRAB domain and several C2H2-type zinc finger motifs. Mutations in this gene cause an X-linked form of intellectual disability (MRX45). Microduplication of a region of chromosome X including this gene has also been associated with other forms of intellectual disability. [provided by RefSeq, Jul 2017]

ZNF81 Gene-Disease associations (from GenCC):

• non-syndromic X-linked intellectual disability

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
• intellectual disability, X-linked 45

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
• X-linked intellectual disability

  Inheritance: XL Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant X-47888091-A-G is Benign according to our data. Variant chrX-47888091-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3047681.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.126 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 2 Unknown,XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007137.5. 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
	ZNF81	NM_007137.5	MANE Select	c.147A>G	p.Val49Val	synonymous	Exon 3 of 5	NP_009068.2	P51508
	ZNF81	NM_001378152.1		c.147A>G	p.Val49Val	synonymous	Exon 4 of 6	NP_001365081.1	P51508
	ZNF81	NM_001378153.1		c.147A>G	p.Val49Val	synonymous	Exon 3 of 5	NP_001365082.1	P51508

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF81	ENST00000338637.13	TSL:3 MANE Select	c.147A>G	p.Val49Val	synonymous	Exon 3 of 5	ENSP00000341151.7	P51508
	ZNF81	ENST00000334937.8	TSL:1	c.147A>G	p.Val49Val	synonymous	Exon 4 of 4	ENSP00000334641.4	B1AJV1
	ZNF81	ENST00000376954.6	TSL:5	c.147A>G	p.Val49Val	synonymous	Exon 4 of 6	ENSP00000366153.1	P51508

Frequencies

GnomAD3 genomes AF: 0.0000904 AC: 10 AN: 110622 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00350

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00429

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000310 AC: 56 AN: 180747 AF XY: 0.000381

Gnomad AFR exome AF: 0.0000777

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: 0.00

Gnomad OTH exome AF: 0.000451

GnomAD4 exome AF: 0.000137 AC: 150 AN: 1097397 Hom.: 0 Cov.: 31 AF XY: 0.000201 AC XY: 73 AN XY: 362815

African (AFR) AF: 0.0000379 AC: 1 AN: 26395

American (AMR) AF: 0.00 AC: 0 AN: 35087

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19374

East Asian (EAS) AF: 0.00 AC: 0 AN: 30183

South Asian (SAS) AF: 0.00256 AC: 138 AN: 54011

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40466

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4116

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841705

Other (OTH) AF: 0.000239 AC: 11 AN: 46060

GnomAD4 genome AF: 0.0000904 AC: 10 AN: 110672 Hom.: 0 Cov.: 22 AF XY: 0.0000608 AC XY: 2 AN XY: 32882

African (AFR) AF: 0.00 AC: 0 AN: 30410

American (AMR) AF: 0.00 AC: 0 AN: 10395

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2632

East Asian (EAS) AF: 0.00 AC: 0 AN: 3507

South Asian (SAS) AF: 0.00351 AC: 9 AN: 2564

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5875

Middle Eastern (MID) AF: 0.00472 AC: 1 AN: 212

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52894

Other (OTH) AF: 0.00 AC: 0 AN: 1499

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	ZNF81-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.1
DANN	Benign	0.56
PhyloP100		-0.13
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs782661971; hg19: chrX-47747490;