22-37074184-T-C

Variant names:

• chr22-37074184-T-C
• rs2413450
• NM_001374504.1:c.1441+426A>G

Variant summary

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

The NM_001374504.1(TMPRSS6):​c.1441+426A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.604 in 152,104 control chromosomes in the GnomAD database, including 29,047 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 0.60 (29047 hom., cov: 33)
• Consequence: TMPRSS6 NM_001374504.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.117
• Publications: 51 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMPRSS6	NM_001374504.1	c.1441+426A>G		intron_variant	Intron 12 of 17	ENST00000676104.1	NP_001361433.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMPRSS6	ENST00000676104.1	c.1441+426A>G		intron_variant	Intron 12 of 17		NM_001374504.1	ENSP00000501573.1

Frequencies

GnomAD3 genomes AF: 0.603 AC: 91712 AN: 151986 Hom.: 29002 Cov.: 33

Gnomad AFR AF: 0.799

Gnomad AMI AF: 0.605

Gnomad AMR AF: 0.495

Gnomad ASJ AF: 0.564

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.565

Gnomad MID AF: 0.561

Gnomad NFE AF: 0.540

Gnomad OTH AF: 0.573

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

GnomAD4 genome AF: 0.604 AC: 91802 AN: 152104 Hom.: 29047 Cov.: 33 AF XY: 0.596 AC XY: 44295 AN XY: 74342

African (AFR) AF: 0.799 AC: 33171 AN: 41504

American (AMR) AF: 0.495 AC: 7563 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.564 AC: 1959 AN: 3472

East Asian (EAS) AF: 0.467 AC: 2413 AN: 5172

South Asian (SAS) AF: 0.439 AC: 2118 AN: 4824

European-Finnish (FIN) AF: 0.565 AC: 5974 AN: 10582

Middle Eastern (MID) AF: 0.565 AC: 165 AN: 292

European-Non Finnish (NFE) AF: 0.540 AC: 36694 AN: 67958

Other (OTH) AF: 0.567 AC: 1194 AN: 2106

Alfa AF: 0.559 Hom.: 85234

Bravo AF: 0.612

Asia WGS AF: 0.423 AC: 1467 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	7.0
DANN	Benign	0.65
PhyloP100		0.12
Mutation Taster		=100/0	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: rs2413450; hg19: chr22-37470224;