rs79816125

Variant names:

• chr22-37074600-G-A
• rs79816125
• NM_001374504.1:c.1441+10C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001374504.1(TMPRSS6):​c.1441+10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0153 in 1,613,528 control chromosomes in the GnomAD database, including 228 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (22 hom., cov: 33)
  • Exomes 𝑓: 0.016 (206 hom.)
• Consequence: TMPRSS6 NM_001374504.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.402
• Publications: 1 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 22-37074600-G-A is Benign according to our data. Variant chr22-37074600-G-A is described in ClinVar as Benign. ClinVar VariationId is 262721.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0121 (1839/152308) while in subpopulation NFE AF = 0.0171 (1166/68022). AF 95% confidence interval is 0.0163. There are 22 homozygotes in GnomAd4. There are 906 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 22 AR gene

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.1441+10C>T		intron	N/A	NP_001361433.1
	TMPRSS6	NM_001289000.2		c.1441+10C>T		intron	N/A	NP_001275929.1
	TMPRSS6	NM_001289001.2		c.1441+10C>T		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.1441+10C>T		intron	N/A	ENSP00000501573.1
	TMPRSS6	ENST00000406856.7	TSL:1	c.1441+10C>T		intron	N/A	ENSP00000384964.1
	TMPRSS6	ENST00000346753.9	TSL:1	c.1441+10C>T		intron	N/A	ENSP00000334962.6

Frequencies

GnomAD3 genomes AF: 0.0121 AC: 1839 AN: 152190 Hom.: 22 Cov.: 33

Gnomad AFR AF: 0.00287

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.0156

Gnomad ASJ AF: 0.00720

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.0181

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0171

Gnomad OTH AF: 0.0115

GnomAD2 exomes AF: 0.0115 AC: 2893 AN: 250666 AF XY: 0.0120

Gnomad AFR exome AF: 0.00279

Gnomad AMR exome AF: 0.00921

Gnomad ASJ exome AF: 0.00607

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.0197

Gnomad NFE exome AF: 0.0169

Gnomad OTH exome AF: 0.0134

GnomAD4 exome AF: 0.0156 AC: 22778 AN: 1461220 Hom.: 206 Cov.: 32 AF XY: 0.0152 AC XY: 11086 AN XY: 726982

African (AFR) AF: 0.00212 AC: 71 AN: 33466

American (AMR) AF: 0.0101 AC: 450 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00651 AC: 170 AN: 26122

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39688

South Asian (SAS) AF: 0.00210 AC: 181 AN: 86224

European-Finnish (FIN) AF: 0.0183 AC: 979 AN: 53396

Middle Eastern (MID) AF: 0.00555 AC: 32 AN: 5766

European-Non Finnish (NFE) AF: 0.0180 AC: 20058 AN: 1111484

Other (OTH) AF: 0.0138 AC: 833 AN: 60376

GnomAD4 genome AF: 0.0121 AC: 1839 AN: 152308 Hom.: 22 Cov.: 33 AF XY: 0.0122 AC XY: 906 AN XY: 74466

African (AFR) AF: 0.00286 AC: 119 AN: 41572

American (AMR) AF: 0.0156 AC: 238 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00720 AC: 25 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4822

European-Finnish (FIN) AF: 0.0181 AC: 192 AN: 10614

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0171 AC: 1166 AN: 68022

Other (OTH) AF: 0.0114 AC: 24 AN: 2112

Alfa AF: 0.0147 Hom.: 31

Bravo AF: 0.0117

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.87
CADD	Benign	5.1
DANN	Benign	0.32
PhyloP100		0.40
Mutation Taster		=100/0	polymorphism

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: rs79816125; hg19: chr22-37470640;