3-52796531-C-T

Variant names:

• chr3-52796531-C-T
• rs9816589
• NM_002217.4:c.165C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_002217.4(ITIH3):​c.165C>T​(p.Thr55Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00333 in 1,613,516 control chromosomes in the GnomAD database, including 162 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (84 hom., cov: 33)
  • Exomes 𝑓: 0.0018 (78 hom.)
• Consequence: ITIH3 NM_002217.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.89
• Publications: 2 publications found

Genes affected

ITIH3 (HGNC:6168): (inter-alpha-trypsin inhibitor heavy chain 3) This gene encodes the heavy chain subunit of the pre-alpha-trypsin inhibitor complex. This complex may stabilize the extracellular matrix through its ability to bind hyaluronic acid. Polymorphisms of this gene may be associated with increased risk for schizophrenia and major depressive disorder. This gene is present in an inter-alpha-trypsin inhibitor family gene cluster on chromosome 3. [provided by RefSeq, Jul 2015]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 3-52796531-C-T is Benign according to our data. Variant chr3-52796531-C-T is described in ClinVar as Benign. ClinVar VariationId is 778084.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.89 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0602 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002217.4. 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
	ITIH3	NM_002217.4	MANE Select	c.165C>T	p.Thr55Thr	synonymous	Exon 3 of 22	NP_002208.3	Q06033-1
	ITIH3	NM_001392019.1		c.165C>T	p.Thr55Thr	synonymous	Exon 3 of 23	NP_001378948.1	A0A994J439
	ITIH3	NM_001392020.1		c.165C>T	p.Thr55Thr	synonymous	Exon 3 of 22	NP_001378949.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITIH3	ENST00000449956.3	TSL:1 MANE Select	c.165C>T	p.Thr55Thr	synonymous	Exon 3 of 22	ENSP00000415769.2	Q06033-1
	ITIH3	ENST00000703834.1		c.165C>T	p.Thr55Thr	synonymous	Exon 3 of 23	ENSP00000515492.1	A0A994J439
	ITIH3	ENST00000889655.1		c.165C>T	p.Thr55Thr	synonymous	Exon 3 of 21	ENSP00000559714.1

Frequencies

GnomAD3 genomes AF: 0.0178 AC: 2714 AN: 152182 Hom.: 83 Cov.: 33

Gnomad AFR AF: 0.0623

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.0115

GnomAD2 exomes AF: 0.00442 AC: 1098 AN: 248604 AF XY: 0.00340

Gnomad AFR exome AF: 0.0647

Gnomad AMR exome AF: 0.00227

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000710

Gnomad OTH exome AF: 0.00265

GnomAD4 exome AF: 0.00182 AC: 2660 AN: 1461216 Hom.: 78 Cov.: 32 AF XY: 0.00156 AC XY: 1133 AN XY: 726866

African (AFR) AF: 0.0643 AC: 2151 AN: 33458

American (AMR) AF: 0.00282 AC: 126 AN: 44680

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000163 AC: 14 AN: 86152

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.00355 AC: 20 AN: 5632

European-Non Finnish (NFE) AF: 0.0000989 AC: 110 AN: 1111732

Other (OTH) AF: 0.00396 AC: 239 AN: 60344

GnomAD4 genome AF: 0.0178 AC: 2717 AN: 152300 Hom.: 84 Cov.: 33 AF XY: 0.0174 AC XY: 1296 AN XY: 74480

African (AFR) AF: 0.0622 AC: 2583 AN: 41548

American (AMR) AF: 0.00653 AC: 100 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68022

Other (OTH) AF: 0.0114 AC: 24 AN: 2114

Alfa AF: 0.00927 Hom.: 30

Bravo AF: 0.0203

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000237

ClinVar

ClinVar submissions as Germline

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	-0.51
CADD	Benign	9.0
DANN	Benign	0.86
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

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: rs9816589; hg19: chr3-52830547;