NM_022065.5:c.3559A>G

Variant names:

• chr2-43505684-T-C
• rs7578597
• NM_022065.5:c.3559A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022065.5(THADA):​c.3559A>G​(p.Thr1187Ala) variant causes a missense change. The variant allele was found at a frequency of 0.109 in 1,593,848 control chromosomes in the GnomAD database, including 11,113 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.14 (1998 hom., cov: 32)
  • Exomes 𝑓: 0.11 (9115 hom.)
• Consequence: THADA NM_022065.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.85
• Publications: 249 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0019688606).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THADA	NM_022065.5	MANE Select	c.3559A>G	p.Thr1187Ala	missense	Exon 24 of 38	NP_071348.3
	THADA	NM_001083953.2		c.3559A>G	p.Thr1187Ala	missense	Exon 24 of 38	NP_001077422.1
	THADA	NM_001345925.2		c.3559A>G	p.Thr1187Ala	missense	Exon 25 of 39	NP_001332854.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THADA	ENST00000405975.7	TSL:1 MANE Select	c.3559A>G	p.Thr1187Ala	missense	Exon 24 of 38	ENSP00000386088.2
	THADA	ENST00000405006.8	TSL:1	c.3559A>G	p.Thr1187Ala	missense	Exon 24 of 38	ENSP00000385995.4
	THADA	ENST00000408045.7	TSL:1	n.*2654A>G		non_coding_transcript_exon	Exon 24 of 30	ENSP00000384172.2

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21313 AN: 152144 Hom.: 1986 Cov.: 32

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.0812

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.00672

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.0481

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.113

GnomAD2 exomes AF: 0.0990 AC: 21766 AN: 219906 AF XY: 0.100

Gnomad AFR exome AF: 0.268

Gnomad AMR exome AF: 0.0564

Gnomad ASJ exome AF: 0.118

Gnomad EAS exome AF: 0.00576

Gnomad FIN exome AF: 0.0510

Gnomad NFE exome AF: 0.104

Gnomad OTH exome AF: 0.0960

GnomAD4 exome AF: 0.106 AC: 153003 AN: 1441586 Hom.: 9115 Cov.: 30 AF XY: 0.107 AC XY: 76205 AN XY: 714672

African (AFR) AF: 0.268 AC: 8918 AN: 33284

American (AMR) AF: 0.0585 AC: 2445 AN: 41790

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 3023 AN: 25678

East Asian (EAS) AF: 0.00779 AC: 308 AN: 39514

South Asian (SAS) AF: 0.135 AC: 11191 AN: 82904

European-Finnish (FIN) AF: 0.0530 AC: 2780 AN: 52468

Middle Eastern (MID) AF: 0.0720 AC: 413 AN: 5740

European-Non Finnish (NFE) AF: 0.107 AC: 117948 AN: 1100458

Other (OTH) AF: 0.100 AC: 5977 AN: 59750

GnomAD4 genome AF: 0.140 AC: 21364 AN: 152262 Hom.: 1998 Cov.: 32 AF XY: 0.134 AC XY: 9984 AN XY: 74450

African (AFR) AF: 0.265 AC: 10992 AN: 41522

American (AMR) AF: 0.0811 AC: 1241 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 442 AN: 3472

East Asian (EAS) AF: 0.00674 AC: 35 AN: 5194

South Asian (SAS) AF: 0.132 AC: 640 AN: 4832

European-Finnish (FIN) AF: 0.0481 AC: 511 AN: 10618

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7188 AN: 68006

Other (OTH) AF: 0.112 AC: 236 AN: 2114

Alfa AF: 0.116 Hom.: 5738

Bravo AF: 0.146

TwinsUK AF: 0.107 AC: 398

ALSPAC AF: 0.115 AC: 444

ESP6500AA AF: 0.260 AC: 968

ESP6500EA AF: 0.110 AC: 897

ExAC AF: 0.0971 AC: 11681

Asia WGS AF: 0.0660 AC: 231 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.014	T
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.73	T
MetaRNN	Benign	0.0020	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		4.9
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.094
Sift	Benign	0.089	T
Sift4G	Benign	0.080	T
Polyphen		0.17	B
Vest4		0.15
ClinPred		0.014	T
GERP RS		5.5
Varity_R		0.26
gMVP		0.52
Mutation Taster		=93/7	polymorphism (auto)

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: rs7578597; hg19: chr2-43732823; COSMIC: COSV57682006; COSMIC: COSV57682006;