rs143086637

Variant names:

• chr17-36486794-G-A
• rs143086637
• NM_004773.4:c.86+9G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-36486794-G-A
• chr17-36486794-G-C
• chr17-36486794-G-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_004773.4(ZNHIT3):​c.86+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00149 in 1,612,584 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0077 (13 hom., cov: 32)
  • Exomes 𝑓: 0.00084 (19 hom.)
• Consequence: ZNHIT3 NM_004773.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.118
• Publications: 0 publications found

Genes affected

ZNHIT3 (HGNC:12309): (zinc finger HIT-type containing 3) Predicted to enable thyroid hormone receptor binding activity. Predicted to be involved in box C/D snoRNP assembly; maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA); and snoRNA localization. Located in cytoplasm and nucleus. Implicated in PEHO syndrome. [provided by Alliance of Genome Resources, Apr 2022]

ZNHIT3 Gene-Disease associations (from GenCC):

• PEHO syndrome

  Inheritance: AR, AD Classification: MODERATE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
• Mayer-Rokitansky-Kuster-Hauser syndrome

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000289011 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 17-36486794-G-A is Benign according to our data. Variant chr17-36486794-G-A is described in ClinVar as Benign. ClinVar VariationId is 710110.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00771 (1174/152268) while in subpopulation AFR AF = 0.0268 (1115/41548). AF 95% confidence interval is 0.0255. There are 13 homozygotes in GnomAd4. There are 564 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 13 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004773.4. 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
	ZNHIT3	NM_004773.4	MANE Select	c.86+9G>A		intron	N/A	NP_004764.1	Q15649-1
	ZNHIT3	NM_001281432.2		c.86+9G>A		intron	N/A	NP_001268361.1	Q15649-2
	ZNHIT3	NM_001281434.2		c.86+9G>A		intron	N/A	NP_001268363.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNHIT3	ENST00000617429.5	TSL:1 MANE Select	c.86+9G>A		intron	N/A	ENSP00000484687.1	Q15649-1
	ZNHIT3	ENST00000619730.4	TSL:1	c.-222+9G>A		intron	N/A	ENSP00000481499.1	A0A087WY42
	ZNHIT3	ENST00000612728.4	TSL:1	n.108+9G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00769 AC: 1170 AN: 152150 Hom.: 13 Cov.: 32

Gnomad AFR AF: 0.0268

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00621

GnomAD2 exomes AF: 0.00198 AC: 490 AN: 247996 AF XY: 0.00141

Gnomad AFR exome AF: 0.0275

Gnomad AMR exome AF: 0.00140

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000358

Gnomad OTH exome AF: 0.000827

GnomAD4 exome AF: 0.000839 AC: 1225 AN: 1460316 Hom.: 19 Cov.: 39 AF XY: 0.000734 AC XY: 533 AN XY: 726558

African (AFR) AF: 0.0298 AC: 987 AN: 33150

American (AMR) AF: 0.00141 AC: 63 AN: 44618

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26078

East Asian (EAS) AF: 0.00 AC: 0 AN: 39490

South Asian (SAS) AF: 0.0000581 AC: 5 AN: 86118

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53362

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5752

European-Non Finnish (NFE) AF: 0.0000495 AC: 55 AN: 1111436

Other (OTH) AF: 0.00179 AC: 108 AN: 60312

GnomAD4 genome AF: 0.00771 AC: 1174 AN: 152268 Hom.: 13 Cov.: 32 AF XY: 0.00758 AC XY: 564 AN XY: 74444

African (AFR) AF: 0.0268 AC: 1115 AN: 41548

American (AMR) AF: 0.00261 AC: 40 AN: 15298

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68014

Other (OTH) AF: 0.00614 AC: 13 AN: 2116

Alfa AF: 0.00403 Hom.: 5

Bravo AF: 0.00842

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.68
CADD	Benign	12
DANN	Benign	0.92
PhyloP100		-0.12
PromoterAI		-0.044	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs143086637; hg19: chr17-34842638;