rs115270691

Variant names:

• chr22-37103525-G-A
• rs115270691
• ENST00000346753.9:c.-13C>T

Your query was ambiguous. Multiple possible variants found:

• chr22-37103525-G-A
• chr22-37103525-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_153609.4(TMPRSS6):​c.-13C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0265 in 1,614,108 control chromosomes in the GnomAD database, including 634 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.025 (64 hom., cov: 32)
  • Exomes 𝑓: 0.027 (570 hom.)
• Consequence: TMPRSS6 NM_153609.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.37
• Publications: 3 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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 22-37103525-G-A is Benign according to our data. Variant chr22-37103525-G-A is described in ClinVar as Benign. ClinVar VariationId is 262723.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0626 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153609.4. 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
	TMPRSS6	NM_001374504.1	MANE Select	c.-1-107C>T		intron	N/A	NP_001361433.1	Q8IU80-1
	TMPRSS6	NM_153609.4		c.-13C>T		5_prime_UTR	Exon 1 of 18	NP_705837.2	Q8IU80-1
	TMPRSS6	NM_001289000.2		c.-1-107C>T		intron	N/A	NP_001275929.1	Q8IU80-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMPRSS6	ENST00000346753.9	TSL:1	c.-13C>T		5_prime_UTR	Exon 1 of 18	ENSP00000334962.6	Q8IU80-1
	TMPRSS6	ENST00000442782.7	TSL:1	c.-13C>T		5_prime_UTR	Exon 1 of 10	ENSP00000397691.3	X6REP5
	TMPRSS6	ENST00000676104.1	MANE Select	c.-1-107C>T		intron	N/A	ENSP00000501573.1	Q8IU80-1

Frequencies

GnomAD3 genomes AF: 0.0246 AC: 3744 AN: 152198 Hom.: 64 Cov.: 32

Gnomad AFR AF: 0.0242

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0308

Gnomad ASJ AF: 0.0309

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00642

Gnomad FIN AF: 0.00433

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0288

Gnomad OTH AF: 0.0401

GnomAD2 exomes AF: 0.0212 AC: 5337 AN: 251246 AF XY: 0.0214

Gnomad AFR exome AF: 0.0247

Gnomad AMR exome AF: 0.0180

Gnomad ASJ exome AF: 0.0299

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00646

Gnomad NFE exome AF: 0.0297

Gnomad OTH exome AF: 0.0269

GnomAD4 exome AF: 0.0267 AC: 38976 AN: 1461792 Hom.: 570 Cov.: 34 AF XY: 0.0263 AC XY: 19137 AN XY: 727198

African (AFR) AF: 0.0239 AC: 800 AN: 33480

American (AMR) AF: 0.0198 AC: 884 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0276 AC: 721 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0114 AC: 984 AN: 86256

European-Finnish (FIN) AF: 0.00622 AC: 332 AN: 53334

Middle Eastern (MID) AF: 0.0681 AC: 393 AN: 5768

European-Non Finnish (NFE) AF: 0.0297 AC: 33072 AN: 1112000

Other (OTH) AF: 0.0296 AC: 1789 AN: 60396

GnomAD4 genome AF: 0.0245 AC: 3739 AN: 152316 Hom.: 64 Cov.: 32 AF XY: 0.0230 AC XY: 1717 AN XY: 74492

African (AFR) AF: 0.0241 AC: 1002 AN: 41568

American (AMR) AF: 0.0308 AC: 471 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0309 AC: 107 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00664 AC: 32 AN: 4822

European-Finnish (FIN) AF: 0.00433 AC: 46 AN: 10618

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0287 AC: 1955 AN: 68028

Other (OTH) AF: 0.0392 AC: 83 AN: 2116

Alfa AF: 0.0236 Hom.: 47

Bravo AF: 0.0271

Asia WGS AF: 0.00491 AC: 17 AN: 3478

EpiCase AF: 0.0323

EpiControl AF: 0.0318

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Microcytic anemia (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.4
DANN	Benign	0.65
PhyloP100		1.4
PromoterAI		0.054	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs115270691; hg19: chr22-37499565;