rs11203200

Positions:

• chr21-42394466-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001256317.3(TMPRSS3):​c.94+858C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0938 in 152,172 control chromosomes in the GnomAD database, including 768 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 0.094 (768 hom., cov: 32)
• Consequence: TMPRSS3 NM_001256317.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.223

Genes affected

TMPRSS3 (HGNC:11877): (transmembrane serine protease 3) This gene encodes a protein that belongs to the serine protease family. The encoded protein contains a serine protease domain, a transmembrane domain, an LDL receptor-like domain, and a scavenger receptor cysteine-rich domain. Serine proteases are known to be involved in a variety of biological processes, whose malfunction often leads to human diseases and disorders. This gene was identified by its association with both congenital and childhood onset autosomal recessive deafness. This gene is expressed in fetal cochlea and many other tissues, and is thought to be involved in the development and maintenance of the inner ear or the contents of the perilymph and endolymph. This gene was also identified as a tumor-associated gene that is overexpressed in ovarian tumors. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jan 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMPRSS3	NM_001256317.3	c.94+858C>T		intron_variant		ENST00000644384.2	NP_001243246.1
TMPRSS3	NM_024022.4	c.94+858C>T		intron_variant			NP_076927.1
TMPRSS3	NM_032405.2	c.94+858C>T		intron_variant			NP_115781.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMPRSS3	ENST00000644384.2	c.94+858C>T		intron_variant			NM_001256317.3	ENSP00000494414.1

Frequencies

GnomAD3 genomes AF: 0.0938 AC: 14268 AN: 152054 Hom.: 770 Cov.: 32

Gnomad AFR AF: 0.0632

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.0893

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.00289

Gnomad SAS AF: 0.0723

Gnomad FIN AF: 0.0772

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.0951

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

GnomAD4 genome AF: 0.0938 AC: 14268 AN: 152172 Hom.: 768 Cov.: 32 AF XY: 0.0914 AC XY: 6803 AN XY: 74396

Gnomad4 AFR AF: 0.0632

Gnomad4 AMR AF: 0.0891

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.00289

Gnomad4 SAS AF: 0.0726

Gnomad4 FIN AF: 0.0772

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.0946

Alfa AF: 0.117 Hom.: 1531

Bravo AF: 0.0918

Asia WGS AF: 0.0490 AC: 170 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.7
DANN	Benign	0.69

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

Publications

LitVar

Other links and lift over

dbSNP: rs11203200; hg19: chr21-43814575;