rs2235321

Variant names:

• chr22-37066886-G-A
• rs2235321
• NM_001374504.1:c.2190C>T

Your query was ambiguous. Multiple possible variants found:

• chr22-37066886-G-A
• chr22-37066886-G-C

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001374504.1(TMPRSS6):​c.2190C>T​(p.Tyr730Tyr) variant causes a synonymous change. The variant allele was found at a frequency of 0.378 in 1,613,618 control chromosomes in the GnomAD database, including 117,508 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.38 (11343 hom., cov: 33)
  • Exomes 𝑓: 0.38 (106165 hom.)
• Consequence: TMPRSS6 NM_001374504.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 3.74
• Publications: 36 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: Labcorp Genetics (formerly Invitae), Orphanet, G2P, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 22-37066886-G-A is Benign according to our data. Variant chr22-37066886-G-A is described in ClinVar as Benign. ClinVar VariationId is 262726.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001374504.1. 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
	TMPRSS6	NM_001374504.1	MANE Select	c.2190C>T	p.Tyr730Tyr	synonymous	Exon 17 of 18	NP_001361433.1
	TMPRSS6	NM_001289000.2		c.2256C>T	p.Tyr752Tyr	synonymous	Exon 18 of 19	NP_001275929.1
	TMPRSS6	NM_001289001.2		c.2190C>T	p.Tyr730Tyr	synonymous	Exon 17 of 18	NP_001275930.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMPRSS6	ENST00000676104.1	MANE Select	c.2190C>T	p.Tyr730Tyr	synonymous	Exon 17 of 18	ENSP00000501573.1
	TMPRSS6	ENST00000406856.7	TSL:1	c.2256C>T	p.Tyr752Tyr	synonymous	Exon 18 of 19	ENSP00000384964.1
	TMPRSS6	ENST00000346753.9	TSL:1	c.2190C>T	p.Tyr730Tyr	synonymous	Exon 17 of 18	ENSP00000334962.6

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58137 AN: 151890 Hom.: 11330 Cov.: 33

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.361

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.478

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.363

GnomAD2 exomes AF: 0.360 AC: 90277 AN: 250550 AF XY: 0.359

Gnomad AFR exome AF: 0.426

Gnomad AMR exome AF: 0.226

Gnomad ASJ exome AF: 0.351

Gnomad EAS exome AF: 0.442

Gnomad FIN exome AF: 0.480

Gnomad NFE exome AF: 0.378

Gnomad OTH exome AF: 0.354

GnomAD4 exome AF: 0.377 AC: 551480 AN: 1461610 Hom.: 106165 Cov.: 55 AF XY: 0.375 AC XY: 272372 AN XY: 727094

African (AFR) AF: 0.421 AC: 14085 AN: 33478

American (AMR) AF: 0.230 AC: 10284 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 9168 AN: 26136

East Asian (EAS) AF: 0.443 AC: 17570 AN: 39690

South Asian (SAS) AF: 0.287 AC: 24740 AN: 86252

European-Finnish (FIN) AF: 0.478 AC: 25517 AN: 53344

Middle Eastern (MID) AF: 0.379 AC: 2184 AN: 5766

European-Non Finnish (NFE) AF: 0.383 AC: 425353 AN: 1111872

Other (OTH) AF: 0.374 AC: 22579 AN: 60374

GnomAD4 genome AF: 0.383 AC: 58180 AN: 152008 Hom.: 11343 Cov.: 33 AF XY: 0.381 AC XY: 28328 AN XY: 74290

African (AFR) AF: 0.419 AC: 17364 AN: 41470

American (AMR) AF: 0.269 AC: 4121 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 1285 AN: 3462

East Asian (EAS) AF: 0.433 AC: 2235 AN: 5160

South Asian (SAS) AF: 0.272 AC: 1307 AN: 4812

European-Finnish (FIN) AF: 0.478 AC: 5050 AN: 10554

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.377 AC: 25626 AN: 67938

Other (OTH) AF: 0.360 AC: 761 AN: 2112

Alfa AF: 0.373 Hom.: 40005

Bravo AF: 0.374

Asia WGS AF: 0.290 AC: 1008 AN: 3478

EpiCase AF: 0.381

EpiControl AF: 0.368

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Iron-refractory iron deficiency anemia (1)
-	-	1	Microcytic anemia (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	7.4
DANN	Benign	0.87
PhyloP100		3.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2235321; hg19: chr22-37462926; COSMIC: COSV60976213; COSMIC: COSV60976213;