rs150193405

Variant names:

• chr4-67838318-C-G
• rs150193405
• NM_004262.3:c.329G>C

Your query was ambiguous. Multiple possible variants found:

• chr4-67838318-C-G
• chr4-67838318-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004262.3(TMPRSS11D):​c.329G>C​(p.Ser110Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000706 in 1,416,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S110N) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: TMPRSS11D NM_004262.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.03
• Publications: 0 publications found

Genes affected

TMPRSS11D (HGNC:24059): (transmembrane serine protease 11D) This gene encodes a trypsin-like serine protease released from the submucosal serous glands onto mucous membrane. It is a type II integral membrane protein and has 29-38% identity in the sequence of the catalytic region with human hepsin, enteropeptidase, acrosin, and mast cell tryptase. The noncatalytic region has little similarity to other known proteins. This protein may play some biological role in the host defense system on the mucous membrane independently of or in cooperation with other substances in airway mucous or bronchial secretions. This protein facilitates entry of viruses into host cells by proteolytically cleaving and activating viral envelope glycoproteins. [provided by RefSeq, Aug 2021]

UBA6-DT (HGNC:49083): (UBA6 divergent transcript)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06250203).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004262.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMPRSS11D	NM_004262.3	MANE Select	c.329G>C	p.Ser110Thr	missense	Exon 5 of 10	NP_004253.1	O60235

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMPRSS11D	ENST00000283916.11	TSL:1 MANE Select	c.329G>C	p.Ser110Thr	missense	Exon 5 of 10	ENSP00000283916.6	O60235
	UBA6-DT	ENST00000500538.7	TSL:1	n.1987+83063C>G		intron	N/A
	TMPRSS11D	ENST00000502573.5	TSL:4	n.187G>C		non_coding_transcript_exon	Exon 3 of 5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.06e-7 AC: 1 AN: 1416038 Hom.: 0 Cov.: 30 AF XY: 0.00000142 AC XY: 1 AN XY: 702766

African (AFR) AF: 0.00 AC: 0 AN: 31100

American (AMR) AF: 0.00 AC: 0 AN: 34430

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24474

East Asian (EAS) AF: 0.00 AC: 0 AN: 38020

South Asian (SAS) AF: 0.00 AC: 0 AN: 77408

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5590

European-Non Finnish (NFE) AF: 9.14e-7 AC: 1 AN: 1093958

Other (OTH) AF: 0.00 AC: 0 AN: 58460

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.010
DANN	Benign	0.71
DEOGEN2	Benign	0.24	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0098	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		-4.0
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.063
Sift	Benign	0.58	T
Sift4G	Benign	0.49	T
Polyphen		0.023	B
Vest4		0.12
MutPred		0.43		Gain of catalytic residue at S110 (P = 0.0803)
MVP		0.23
MPC		0.084
ClinPred		0.045	T
GERP RS		-6.3
PromoterAI		-0.032	Neutral
Varity_R		0.051
gMVP		0.16
Mutation Taster		=97/3	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: rs150193405; hg19: chr4-68704036;