chr22-37071352-G-C

Variant names:

• chr22-37071352-G-C
• rs5756506
• NM_001374504.1:c.1556-320C>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.1556-320C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 151,998 control chromosomes in the GnomAD database, including 18,834 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 0.47 (18834 hom., cov: 32)
• Consequence: TMPRSS6 NM_001374504.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.218
• Publications: 37 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.733 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.1556-320C>G		intron	N/A	NP_001361433.1
	TMPRSS6	NM_001289000.2		c.1556-320C>G		intron	N/A	NP_001275929.1
	TMPRSS6	NM_001289001.2		c.1556-320C>G		intron	N/A	NP_001275930.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMPRSS6	ENST00000676104.1	MANE Select	c.1556-320C>G		intron	N/A	ENSP00000501573.1
	TMPRSS6	ENST00000406856.7	TSL:1	c.1556-320C>G		intron	N/A	ENSP00000384964.1
	TMPRSS6	ENST00000346753.9	TSL:1	c.1556-320C>G		intron	N/A	ENSP00000334962.6

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70612 AN: 151880 Hom.: 18800 Cov.: 32

Gnomad AFR AF: 0.740

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.455

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.426

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

GnomAD4 genome AF: 0.465 AC: 70690 AN: 151998 Hom.: 18834 Cov.: 32 AF XY: 0.459 AC XY: 34088 AN XY: 74292

African (AFR) AF: 0.740 AC: 30690 AN: 41454

American (AMR) AF: 0.302 AC: 4610 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 1355 AN: 3472

East Asian (EAS) AF: 0.456 AC: 2347 AN: 5150

South Asian (SAS) AF: 0.263 AC: 1268 AN: 4822

European-Finnish (FIN) AF: 0.415 AC: 4383 AN: 10552

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.363 AC: 24688 AN: 67944

Other (OTH) AF: 0.422 AC: 892 AN: 2114

Alfa AF: 0.229 Hom.: 453

Bravo AF: 0.474

Asia WGS AF: 0.324 AC: 1125 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.5
DANN	Benign	0.65
PhyloP100		-0.22
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: rs5756506; hg19: chr22-37467392;