NM_022065.5:c.5656_5658delTTC

Variant names:

• chr2-43231151-TGAA-T
• rs544375407
• NM_022065.5:c.5656_5658delTTC

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 1P and 6B. PM4_Supporting BP6_Moderate BS2

The NM_022065.5(THADA):​c.5656_5658delTTC​(p.Phe1886del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00265 in 1,613,918 control chromosomes in the GnomAD database, including 13 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0023 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (11 hom.)
• Consequence: THADA NM_022065.5 conservative_inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 3.24
• Publications: 0 publications found

Genes affected

THADA (HGNC:19217): (THADA armadillo repeat containing) This gene is the target of 2p21 choromosomal aberrations in benign thyroid adenomas. Single nucleotide polymorphisms (SNPs) in this gene may be associated with type 2 diabetes and polycystic ovary syndrome. The encoded protein is likely involved in the death receptor pathway and apoptosis. [provided by RefSeq, Sep 2016]

LINC01126 (HGNC:49275): (long intergenic non-protein coding RNA 1126)

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_022065.5. Strenght limited to Supporting due to length of the change: 1aa.
• BP6: Variant 2-43231151-TGAA-T is Benign according to our data. Variant chr2-43231151-TGAA-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2650853.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022065.5. 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
	THADA	NM_022065.5	MANE Select	c.5656_5658delTTC	p.Phe1886del	conservative_inframe_deletion	Exon 38 of 38	NP_071348.3
	THADA	NM_001083953.2		c.5656_5658delTTC	p.Phe1886del	conservative_inframe_deletion	Exon 38 of 38	NP_001077422.1	Q6YHU6-1
	THADA	NM_001345925.2		c.5656_5658delTTC	p.Phe1886del	conservative_inframe_deletion	Exon 39 of 39	NP_001332854.1	Q6YHU6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THADA	ENST00000405975.7	TSL:1 MANE Select	c.5656_5658delTTC	p.Phe1886del	conservative_inframe_deletion	Exon 38 of 38	ENSP00000386088.2	Q6YHU6-1
	THADA	ENST00000405006.8	TSL:1	c.5656_5658delTTC	p.Phe1886del	conservative_inframe_deletion	Exon 38 of 38	ENSP00000385995.4	Q6YHU6-1
	THADA	ENST00000855634.1		c.5656_5658delTTC	p.Phe1886del	conservative_inframe_deletion	Exon 39 of 39	ENSP00000525693.1

Frequencies

GnomAD3 genomes AF: 0.00227 AC: 345 AN: 152178 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000362

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0162

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00223

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00266 AC: 661 AN: 248924 AF XY: 0.00258

Gnomad AFR exome AF: 0.000388

Gnomad AMR exome AF: 0.000348

Gnomad ASJ exome AF: 0.0000994

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0156

Gnomad NFE exome AF: 0.00259

Gnomad OTH exome AF: 0.00199

GnomAD4 exome AF: 0.00269 AC: 3937 AN: 1461622 Hom.: 11 AF XY: 0.00256 AC XY: 1859 AN XY: 727080

African (AFR) AF: 0.000358 AC: 12 AN: 33480

American (AMR) AF: 0.000291 AC: 13 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26134

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

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86236

European-Finnish (FIN) AF: 0.0138 AC: 737 AN: 53402

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

European-Non Finnish (NFE) AF: 0.00278 AC: 3089 AN: 1111818

Other (OTH) AF: 0.00139 AC: 84 AN: 60372

GnomAD4 genome AF: 0.00227 AC: 345 AN: 152296 Hom.: 2 Cov.: 32 AF XY: 0.00277 AC XY: 206 AN XY: 74458

African (AFR) AF: 0.000361 AC: 15 AN: 41574

American (AMR) AF: 0.000392 AC: 6 AN: 15304

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.0162 AC: 172 AN: 10614

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

European-Non Finnish (NFE) AF: 0.00223 AC: 152 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.00210 Hom.: 0

Bravo AF: 0.00122

EpiCase AF: 0.00207

EpiControl AF: 0.00249

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	THADA-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.2
Mutation Taster		=88/12	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: rs544375407; hg19: chr2-43458290; COSMIC: COSV56700407; COSMIC: COSV56700407;