22-37078039-G-A

Variant names:

• chr22-37078039-G-A
• rs855788
• NM_001374504.1:c.1197-2759C>T

Variant summary

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

The NM_001374504.1(TMPRSS6):​c.1197-2759C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.499 in 152,086 control chromosomes in the GnomAD database, including 22,039 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 0.50 (22039 hom., cov: 32)
• Consequence: TMPRSS6 NM_001374504.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.39
• Publications: 12 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

LOC124905113 (HGNC:):

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 = 0.809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMPRSS6	NM_001374504.1	c.1197-2759C>T		intron_variant	Intron 10 of 17	ENST00000676104.1	NP_001361433.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMPRSS6	ENST00000676104.1	c.1197-2759C>T		intron_variant	Intron 10 of 17		NM_001374504.1	ENSP00000501573.1

Frequencies

GnomAD3 genomes AF: 0.499 AC: 75827 AN: 151968 Hom.: 22005 Cov.: 32

Gnomad AFR AF: 0.816

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.448

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

GnomAD4 genome AF: 0.499 AC: 75909 AN: 152086 Hom.: 22039 Cov.: 32 AF XY: 0.496 AC XY: 36832 AN XY: 74332

African (AFR) AF: 0.816 AC: 33857 AN: 41486

American (AMR) AF: 0.327 AC: 5000 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.342 AC: 1187 AN: 3468

East Asian (EAS) AF: 0.323 AC: 1666 AN: 5152

South Asian (SAS) AF: 0.345 AC: 1665 AN: 4826

European-Finnish (FIN) AF: 0.441 AC: 4663 AN: 10574

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.390 AC: 26504 AN: 67976

Other (OTH) AF: 0.443 AC: 936 AN: 2114

Alfa AF: 0.420 Hom.: 14187

Bravo AF: 0.505

Asia WGS AF: 0.319 AC: 1107 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	0.37
DANN	Benign	0.48
PhyloP100		-2.4
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: rs855788; hg19: chr22-37474079;