rs228921

Variant names:

• chr22-37110836-A-G
• rs228921
• ENST00000862824.1:c.-383T>C

Variant summary

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

The ENST00000862824.1(TMPRSS6):​c.-383T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 151,914 control chromosomes in the GnomAD database, including 12,640 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 0.41 (12640 hom., cov: 32)
• Consequence: TMPRSS6 ENST00000862824.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 8 publications found

Genes affected

TMPRSS6 (HGNC:16517): (transmembrane serine protease 6) The protein encoded by this gene is a type II transmembrane serine proteinase that is found attached to the cell surface. The encoded protein may be involved in matrix remodeling processes in the liver. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

TMPRSS6 Gene-Disease associations (from GenCC):

• IRIDA syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P, ClinGen, PanelApp Australia, Orphanet

ENSG00000294412 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000862824.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMPRSS6	ENST00000862824.1		c.-383T>C		5_prime_UTR	Exon 1 of 18	ENSP00000532883.1
	ENSG00000294412	ENST00000723443.1		n.*160A>G		downstream_gene	N/A
	ENSG00000294412	ENST00000723444.1		n.*160A>G		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61565 AN: 151796 Hom.: 12611 Cov.: 32

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.402

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.397

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.406 AC: 61644 AN: 151914 Hom.: 12640 Cov.: 32 AF XY: 0.407 AC XY: 30227 AN XY: 74258

African (AFR) AF: 0.388 AC: 16060 AN: 41420

American (AMR) AF: 0.338 AC: 5168 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.402 AC: 1396 AN: 3470

East Asian (EAS) AF: 0.398 AC: 2048 AN: 5152

South Asian (SAS) AF: 0.485 AC: 2336 AN: 4814

European-Finnish (FIN) AF: 0.438 AC: 4607 AN: 10528

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.424 AC: 28792 AN: 67944

Other (OTH) AF: 0.402 AC: 849 AN: 2110

Alfa AF: 0.415 Hom.: 32616

Bravo AF: 0.393

Asia WGS AF: 0.485 AC: 1690 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.20
PhyloP100		-1.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs228921; hg19: chr22-37506876;